Zespół paznokciowo-patellarny – Etiologia i przyczyny

Zespół paznokciowo-patellarny
Etiologia i przyczyny

Zespół paznokciowo-patellarny (NPS) jest rzadkim, autosomalnie dominującym zaburzeniem genetycznym spowodowanym mutacjami w genie LMX1B (9q34.1), kodującym czynnik transkrypcyjny LIM-homeodomenowy. Mutacje te prowadzą do haploinsuficjencji białka LMX1B, co skutkuje zaburzeniami rozwojowymi w obrębie paznokci, rzepek, stawów łokciowych, miednicy oraz narządów takich jak nerki i oczy. W patogenezie kluczową rolę odgrywa dysfunkcja podocytów i błony podstawnej kłębuszków nerkowych, co może manifestować się jako nefropatia, w tym izolowane FSGS10 (ogniskowe segmentowe stwardnienie kłębuszków nerkowych typu 10). Pełna penetracja genowa NPS współistnieje ze zmienną ekspresyjnością fenotypową, a około 10-20% przypadków wynika z mutacji de novo. Diagnostyka opiera się na obrazie klinicznym oraz potwierdzeniu mutacji w genie LMX1B, przy czym u około 9% rodzin z objawami NPS nie wykryto mutacji w tym genie, co sugeruje heterogenność genetyczną zespołu.

Etiologia zespołu paznokciowo-patellarnego

Zespół paznokciowo-patellarny (ang. Nail-Patella Syndrome, NPS) jest rzadkim zaburzeniem genetycznym charakteryzującym się nieprawidłowościami w obrębie paznokci, rzepek, stawów łokciowych, miednicy oraz potencjalnie innych narządów, takich jak nerki i oczy. Główną przyczyną tej choroby są mutacje w genie LMX1B, które prowadzą do zaburzeń rozwojowych struktur ciała podczas życia płodowego.¹²

Mutacje genu LMX1B jako główna przyczyna

Gen LMX1B zlokalizowany jest na długim ramieniu chromosomu 9 (9q34.1) i koduje czynnik transkrypcyjny należący do rodziny białek LIM-homeodomenowych.³⁴ Białko LMX1B odgrywa kluczową rolę w rozwoju wielu tkanek i narządów, w tym:

Formowaniu struktur grzbietowo-brzusznych kończyn
Różnicowaniu neuronów dopaminergicznych i serotoninergicznych
Kształtowaniu czaszki
Rozwoju mezenchymy okołogałkowej
Rozwoju podocytów nerkowych⁵⁶

Zidentyfikowano co najmniej 142 różne mutacje w genie LMX1B prowadzące do zespołu paznokciowo-patellarnego.⁷ Mutacje te powodują produkcję nieprawidłowo skróconego, niefunkcjonalnego białka lub zaburzają zdolność białka do wiązania się z DNA.⁸⁹ Skutkuje to zaburzeniami w regulacji aktywności innych genów i prowadzi do nieprawidłowości rozwojowych.

Mechanizm patogenetyczny

Głównym mechanizmem patogenetycznym w zespole paznokciowo-patellarnym jest haploinsuficjencja, czyli stan, w którym jedna kopia genu jest niewystarczająca do produkcji odpowiedniej ilości białka potrzebnego do prawidłowego funkcjonowania organizmu.¹⁰¹¹ Badania przeprowadzone na myszach z wyłączonym genem Lmx1b oraz testy in vitro wykazały, że białko LMX1B ekspresjonowane w podocytach kłębuszków nerkowych pomaga kontrolować transkrypcję wielu genów niezbędnych do prawidłowego formowania błony podstawnej kłębuszków (GBM) i/lub różnicowania i funkcjonowania podocytów kłębuszkowych we wczesnych stadiach rozwoju nerek.¹²

Identyfikacja całkowitych delecji LMX1B potwierdza, że haploinsuficjencja jest głównym mechanizmem patogenetycznym NPS.¹³ Większość pacjentów ma mutacje lub delecje LMX1B odpowiedzialne za haploinsuficjencję poprzez szlak nonsense-mediated mRNA decay.¹⁴

Sposób dziedziczenia

Zespół paznokciowo-patellarny dziedziczy się w sposób autosomalny dominujący, co oznacza, że jedna zmutowana kopia genu LMX1B w każdej komórce jest wystarczająca do wywołania choroby.¹⁵¹⁶ Rodzic z zespołem paznokciowo-patellarnym ma 50% szans przekazania zmutowanego genu dziecku, niezależnie od jego płci.¹⁷¹⁸

Choroba wykazuje pełną penetrację genową (ujawnia się u każdej osoby z mutacją), ale jednocześnie zmienną ekspresyjność, co oznacza, że nasilenie objawów może być różne nawet wśród członków tej samej rodziny.¹⁹²⁰

Mutacje de novo

Nie zawsze zespół paznokciowo-patellarny jest dziedziczony od rodziców. W około 10-20% przypadków choroba jest wynikiem spontanicznej mutacji de novo, gdy żadne z rodziców nie ma zespołu paznokciowo-patellarnego.²¹²²²³ W takich przypadkach mutacja w genie LMX1B pojawia się po raz pierwszy w komórce jajowej lub plemnikach rodzica albo podczas wczesnego rozwoju zarodka.²⁴

Możliwość mozaicyzmu somatycznego

Istnieją dowody na występowanie mozaicyzmu somatycznego w zespole paznokciowo-patellarnym, co oznacza, że niektóre komórki organizmu mają mutację genetyczną powodującą zespół, podczas gdy inne jej nie mają.²⁵²⁶ Zjawisko to może występować u rodziców, którzy nie mają objawów zespołu, ale mają dziecko z NPS, co jest znanym zjawiskiem w chorobach autosomalnych dominujących.²⁷

Heterogenność genetyczna i interakcje genowe

Potencjalna heterogenność genetyczna

Choć mutacje w genie LMX1B są główną przyczyną zespołu paznokciowo-patellarnego, u niektórych pacjentów z objawami typowymi dla NPS nie wykryto zmian w tym genie.²⁸ W badaniu obejmującym 55 rodzin z NPS, u około 9% rodzin nie zidentyfikowano żadnych zmian genomowych w genie LMX1B pomimo szczegółowej analizy regionów kodujących i niekodujących.²⁹

W jednej z rodzin nie wykazano sprzężenia z locus LMX1B (9q33.3), co sugeruje, że alteracja genomowa tego genu nie jest zaangażowana w tej konkretnej rodzinie i podnosi hipotezę o heterogenności genetycznej zespołu paznokciowo-patellarnego.³⁰ Naukowcy kontynuują poszukiwania dodatkowych genów, które mogą być związane z tym zespołem.³¹

Interakcje z innymi genami

Innym czynnikiem przyczyniającym się do różnorodności objawów klinicznych w zespole paznokciowo-patellarnym mogą być interakcje między homeodomeną LMX1B a innymi genami.³² Czynnik transkrypcyjny PAX2 został zbadany pod kątem jego interakcji z LMX1B, ponieważ oba białka są zaangażowane w rozwój nerek i oczu.³³³⁴

Wykazano, że mutacje w homeodomenie genu LMX1B wpływają na interakcje z PAX2, co rodzi pytanie o rolę tego ostatniego w zmienności fenotypowej NPS, chociaż potrzebne są dalsze badania, aby przetestować tę możliwość.³⁵³⁶

Delecje LARM2

Zidentyfikowano rodziny z objawami zespołu paznokciowo-patellarnego, u których wykryto delecje LARM2 (LMX1B-associated regulatory module 2) segregujące z cechami klinicznymi NPS, co dodatkowo podkreśla, że delecje LARM2 są odpowiedzialne za część nierozwiązanych rodzinnych przypadków NPS.³⁷ Rodziny te wykazują łagodniejsze formy NPS, co dodatkowo wyjaśnia zmienną ekspresyjność tego zespołu.³⁸

Czynniki wpływające na ekspresję fenotypową

Brak korelacji genotyp-fenotyp

Mimo zidentyfikowania wielu różnych mutacji w genie LMX1B, nie ustalono jasnej korelacji między konkretną mutacją a zakresem i nasileniem objawów zespołu paznokciowo-patellarnego.³⁹⁴⁰ Zespół ten charakteryzuje się wysoką penetracją, ale znaczną zmiennością między- i wewnątrzrodzinną, co przyczynia się do różnorodności objawów klinicznych.⁴¹

Potencjalny wpływ czynników środowiskowych

Niektórzy badacze sugerują, że czynniki środowiskowe mogą również odgrywać rolę w nasileniu objawów zespołu paznokciowo-patellarnego. Czynniki takie jak odżywianie, ekspozycja na toksyny i ogólny stan zdrowia podczas ciąży mogą potencjalnie wpływać na ekspresję zespołu.⁴² Jednak potrzebne są dalsze badania, aby w pełni zrozumieć te interakcje.⁴³

Związek z grupą krwi ABO

Interesującym aspektem zespołu paznokciowo-patellarnego jest jego powiązanie z locus grupy krwi ABO.⁴⁴⁴⁵ Zaburzenie to jest sprzężone z locus grupy krwi ABO, co może mieć znaczenie przy analizie rodzinnego występowania choroby.⁴⁶

Zespół paznokciowo-patellarny a inne zespoły chorobowe

Nerkopochodny zespół podobny do NPS

Heterozygotyczne mutacje w genie LMX1B mogą również powodować izolowaną nefropatię, znaną jako FSGS10 (ogniskowe segmentowe stwardnienie kłębuszków nerkowych typu 10) lub chorobę nerkopodobną zespołu paznokciowo-patellarnego (Nail-patella-like renal disease, NPLRD).⁴⁷⁴⁸ W tej formie choroby pacjenci prezentują zajęcie nerek bez manifestacji szkieletowych lub pozanerkowych.⁴⁹

Biopsje nerek u osób z NPLRD są niejednorodne i mogą wykazywać zmiany minimalne, prawidłowy obraz w mikroskopii elektronowej, zatarcie wypustek podocytów lub zmiany typu FSGS.⁵⁰ Przypadki te wskazują, że choroby związane z LMX1B powinny być brane pod uwagę w diagnostyce różnicowej pacjentów z biopsją nerek wykazującą ciałka mieloidalne w mikroskopii elektronowej.⁵¹

Powiązane zespoły chorobowe

Zespół paznokciowo-patellarny jest również znany pod innymi nazwami, takimi jak:

Zespół Fonga (choroba Fonga)
Zespół Turnera-Kiesera
Dziedziczna osteo-onychodysplazja (HOOD)
Zespół rogów biodrowych⁵²⁵³⁵⁴

Zespół paznokciowo-patellarny jest związany z niedoczynnością tarczycy, zespołem jelita drażliwego, zespołem nadpobudliwości psychoruchowej z deficytem uwagi (ADHD) oraz cienkim szkliwem zębowym. Dokładny charakter tych powiązań pozostaje niejasny.⁵⁵

Postępy w badaniach i diagnostyce

Identyfikacja genu LMX1B

Gen odpowiedzialny za zespół paznokciowo-patellarny został zidentyfikowany przez badaczy z Baylor College of Medicine i M.D. Anderson Cancer Center w Houston.⁵⁶ Dreyer i wsp. (1998) wykazali, że gen LMX1B mapuje do regionu 9q w tym samym obszarze co locus NPS przy użyciu fluorescencyjnej hybrydyzacji in situ.⁵⁷

Ponadto wykazali, że trzech niespokrewnionych pacjentów z NPS miało de novo heterozygotyczne mutacje w tym genie.⁵⁸ Były to pierwsze opisane mutacje w białku LIM-homeodomenowym, które odpowiadały za dziedziczną formę nieprawidłowego kształtowania szkieletu i niewydolność nerek.⁵⁹

Badania nad fenotypem neurologicznym

Zespół paznokciowo-patellarny może również powodować problemy neurologiczne, które mogą być związane z nieprawidłowościami wzorców grzbietowo-brzusznych rozwijającej się kończyny, w tym nieprawidłową migracją neuronalną.⁶⁰ Alternatywnie, objawy neurologiczne mogą wynikać z pierwotnej dysfunkcji LMX1B w obrębie obwodu czuciowego.⁶¹

Wzór ekspresji lmx1b obserwowany w kończynach, oczach i nerkach koreluje z rozpoznanymi objawami i symptomami NPS.⁶² U osób z NPS niedobór projekcji włókien A i C do blaszek I i II może być związany z bólem neuropatycznym, mrowieniem i upośledzonym odczuwaniem ukłucia i zimna obserwowanym w badaniach.⁶³

Rozwój metod diagnostycznych

Zespół paznokciowo-patellarny jest zazwyczaj diagnozowany na podstawie charakterystycznych cech klinicznych, takich jak nieprawidłowości paznokci, rzepek, stawów łokciowych i miednicy.⁶⁴ Jednak w przypadkach niepewnej diagnozy klinicznej lub u osób z atypowymi formami NPS, analiza genetyczna LMX1B może być informacyjna.⁶⁵

Testy obrazowe mogą umożliwić wykrycie NPS prenatalnie w niektórych przypadkach. Inne przypadki mogą nie zostać zdiagnozowane do czasu urodzenia lub wczesnego dzieciństwa, gdy rozwiną się nieprawidłowości paznokci i inne powiązane anomalie.⁶⁶

Gdy podejrzewa się zespół paznokciowo-patellarny, badania genetyczne w kierunku mutacji LMX1B potwierdzają rozpoznanie.⁶⁷ Dzięki postępom w technologiach sekwencjonowania możliwe jest dokładniejsze wykrywanie różnych typów mutacji w genie LMX1B, co przyczynia się do lepszego zrozumienia mechanizmów molekularnych leżących u podstaw tego zespołu.

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Materiały źródłowe

#1 Nail-patella syndrome: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/nail-patella-syndrome/
Nail-patella syndrome is characterized by abnormalities of the nails, knees, elbows, and pelvis. […] Mutations in the LMX1B gene cause nail-patella syndrome. The LMX1B gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. […] Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein’s ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome. […] Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
#2 Nail-patella syndrome | About the Disease | GARD
https://rarediseases.info.nih.gov/diseases/7160/nail-patella-syndrome
Nail-patella syndrome is caused by genetic changes (pathogenic variants) in the LMX1B gene. […] Nail-patella syndrome is caused by genetic mutations, also known as pathogenic variants. […] This disease is caused by a change in the genetic material (DNA). […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.
#3 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#4 Nailâpatella syndrome – Wikipedia
https://en.wikipedia.org/wiki/Nail%E2%80%93patella_syndrome
Causes mutations in the LMX1B gene. […] Nailpatella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9’s q arm (the longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for the disorder to be expressed in the offspring, meaning the chance of getting the disorder from an affected heterozygous parent is 50%. The frequency of the occurrence is 1/50,000. The disorder is linked to the ABO blood group locus. […] It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified. […] The lack of development or complete absence of fingernails results from the loss of function mutations in the LMX1B gene. This mutation may cause a reduction in dorsalising signals, which then results in the failure to normally develop dorsal specific structures such as nails and patellae.
#5 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#6 Nail-Patella Syndrome | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/25513
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. […] At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#7 Nail-Patella Syndrome – MD Searchlight
https://mdsearchlight.com/genetic-disorders/nail-patella-syndrome/
Nail-patella syndrome is an inherited disorder that is passed from parents to children. It is caused by a mutation in a specific gene called LMXB1, which resides on a particular section of chromosome 9. The LMXB1 gene is responsible for creating a protein that plays a critical role in the development of numerous body parts during embryonic stages, including certain parts of limbs, types of brain cells, skull structure, development around the eyes, and specific kidney cells. […] It is known that at least 142 types of changes or mutations in the LMXB1 gene can cause this syndrome. There is also evidence of what is known as somatic mosaicism, a condition where some cells have the genetic mutation causing the syndrome, while others do not. This often happens in parents who do not have the syndrome, but have a child who does.
#8 Nail-patella syndrome: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/nail-patella-syndrome/
Nail-patella syndrome is characterized by abnormalities of the nails, knees, elbows, and pelvis. […] Mutations in the LMX1B gene cause nail-patella syndrome. The LMX1B gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. […] Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein’s ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome. […] Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
#9 Azthena logo with the word Azthena
https://www.news-medical.net/health/Nail-Patella-Syndrome-Features.aspx
Nail patella syndrome is a genetic disorder which results in abnormal development of an individuals nails, kneecaps, elbows and pelvis. […] NPS is caused by mutations in the LMX1B gene which encodes a binding protein for specific areas of the DNA. The mutation produces short and non-functional protein that affects its ability to bind to the DNA. More studies are required to find out exactly how the mutations in the LMX1B gene lead to NPS.
#10 Nail-patella syndrome – UpToDate
https://www.uptodate.com/contents/nail-patella-syndrome
The identification of entire LMX1B deletions confirms that haploinsufficiency is the principal pathogenetic mechanism of NPS. […] Studies in homozygous knock-out mice and in vitro assays demonstrated that LMX1B protein expressed in glomerular podocytes helps control the transcription of multiple genes integral for proper glomerular basement membrane (GBM) formation, and/or glomerular podocyte differentiation and function during the early stages of kidney development.
#11
https://www.omim.org/entry/161200
The LIM-homeodomain protein Lmx1b plays a central role in dorsal/ventral patterning of the vertebrate limb. Targeted disruption of Lmx1b results in skeletal defects, including hypoplastic nails, absent patellae, and a unique form of renal dysplasia (Chen et al., 1998). […] Dreyer et al. (1998) showed that the LMX1B gene maps to 9q in the same region as the NPS locus by fluorescence in situ hybridization. Furthermore, they demonstrated that 3 unrelated NPS patients carried de novo heterozygous mutations in this gene. […] These were the first described mutations in a LIM-homeodomain protein that accounted for an inherited form of abnormal skeletal patterning and renal failure. […] Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene (602575.0013) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome.
#12 Nail-patella syndrome – UpToDate
https://www.uptodate.com/contents/nail-patella-syndrome
The identification of entire LMX1B deletions confirms that haploinsufficiency is the principal pathogenetic mechanism of NPS. […] Studies in homozygous knock-out mice and in vitro assays demonstrated that LMX1B protein expressed in glomerular podocytes helps control the transcription of multiple genes integral for proper glomerular basement membrane (GBM) formation, and/or glomerular podocyte differentiation and function during the early stages of kidney development.
#13
https://www.omim.org/entry/161200
The LIM-homeodomain protein Lmx1b plays a central role in dorsal/ventral patterning of the vertebrate limb. Targeted disruption of Lmx1b results in skeletal defects, including hypoplastic nails, absent patellae, and a unique form of renal dysplasia (Chen et al., 1998). […] Dreyer et al. (1998) showed that the LMX1B gene maps to 9q in the same region as the NPS locus by fluorescence in situ hybridization. Furthermore, they demonstrated that 3 unrelated NPS patients carried de novo heterozygous mutations in this gene. […] These were the first described mutations in a LIM-homeodomain protein that accounted for an inherited form of abnormal skeletal patterning and renal failure. […] Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene (602575.0013) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome.
#14 NailâPatella Syndrome: clinical and molecular data in 55 families raising the hypothesis of a genetic heterogeneity | European Journal of Human Genetics
https://www.nature.com/articles/ejhg201577
NailPatella Syndrome (NPS) is due to variants affecting function in LMX1B, which encodes a LIM-homeodomain protein critical for limb, kidney and eye development. […] The main pathogenic mechanism underlying autosomal dominant NPS in humans is haploinsufficiency. […] The majority of patients carry either LMX1B variants or complete or partial deletions responsible for haploinsufficiency through the nonsense-mediated mRNA decay pathway. […] In the present study, we describe the phenotype and molecular data of 55 index patients and their 39 relatives affected with NPS. […] In 9% of families are not carriers of a LMX1B genomic alteration after extensive study of the coding and non-coding regions of the gene. […] One of the families showed no linkage to the LMX1B locus, raising the hypothesis of a genetic heterogeneity.
#15 Nail-patella syndrome: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/nail-patella-syndrome/
Nail-patella syndrome is characterized by abnormalities of the nails, knees, elbows, and pelvis. […] Mutations in the LMX1B gene cause nail-patella syndrome. The LMX1B gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. […] Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein’s ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome. […] Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
#16 Nail patella syndrome: Causes, symptoms, treatment, inheritance
https://www.medicalnewstoday.com/articles/nail-patella-syndrome
NPS is an autosomal dominant genetic condition. […] Currently, the only known cause of NPS is a change, or mutation, in the LMX1B gene. Mutations in this gene cause changes and irregularities in the skeleton. […] However, about 10% of all new NPS cases occur as a spontaneous mutation when neither parent has the condition. […] There is no correlation between the specific mutation and the range and severity of the condition.
#17 Nail-patella syndrome | About the Disease | GARD
https://rarediseases.info.nih.gov/diseases/7160/nail-patella-syndrome
Nail-patella syndrome is caused by genetic changes (pathogenic variants) in the LMX1B gene. […] Nail-patella syndrome is caused by genetic mutations, also known as pathogenic variants. […] This disease is caused by a change in the genetic material (DNA). […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.
#18 Nail Patella Syndrome: Understanding Symptoms, Causes, and Management â¢ Yesil Health
https://yesilhealth.com/your-health/nail-patella-syndrome-understanding-symptoms-causes-and-management/
Nail Patella Syndrome (NPS) is a rare genetic disorder that primarily affects the development of nails, knees, and other skeletal structures. This condition is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene from an affected parent can cause the disorder in their offspring. The gene responsible for NPS is located on chromosome 9, and its mutation can lead to a variety of physical abnormalities. […] The primary cause of Nail Patella Syndrome is a mutation in the LMX1B gene. This gene plays a vital role in the development of various tissues in the body, particularly those related to the skeletal system. When a mutation occurs, it can lead to the characteristic features of NPS, including: […] Nail Patella Syndrome is inherited in an autosomal dominant manner. This means that only one copy of the mutated gene from an affected parent can cause the syndrome in their offspring. If a parent has NPS, there is a 50% chance that each child will inherit the condition.
#19 Nail-patella syndrome – UpToDate
https://www.uptodate.com/contents/nail-patella-syndrome
Nail-patella syndrome (NPS, MIM #161200) or hereditary osteo-onychodysplasia (HOOD syndrome) is a rare autosomal dominant disorder. It is characterized by limb and pelvic skeletal abnormalities (eg, hypoplastic or absent patella, dysplasia of elbows, including pterygia, and iliac horns), nail and distal digital abnormalities, and kidney disease. […] NPS is an autosomal dominant disorder with full gene penetrance but variability of expression even within families. […] Approximately 85 percent of families with NPS present with mutations of the LMX1B gene located at the distal end of the long arm of chromosome 9. LMX1B is a transcription factor of the LIM-homeodomain type that plays an important role for limb and kidney development in vertebrates; however, it is expressed lifelong within the podocyte and it is essential for the maintenance the structured actin cytoskeleton in podocytes.
#20 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#21
https://111.wales.nhs.uk/nailpatellasyndrome/
Nail patella syndrome is usually caused by a fault in a gene called LMX1B that’s inherited from one parent. […] But there isn’t always a family history of nail patella syndrome. In some cases, an LMX1B gene mutation (alteration) occurs for the first time on its own.
#22 Nail patella syndrome: Causes, symptoms, treatment, inheritance
https://www.medicalnewstoday.com/articles/nail-patella-syndrome
NPS is an autosomal dominant genetic condition. […] Currently, the only known cause of NPS is a change, or mutation, in the LMX1B gene. Mutations in this gene cause changes and irregularities in the skeleton. […] However, about 10% of all new NPS cases occur as a spontaneous mutation when neither parent has the condition. […] There is no correlation between the specific mutation and the range and severity of the condition.
#23 Nail-Patella Syndrome – symptoms, Definition, Description, Demographics, Causes and symptoms, Diagnosis, Treatment
http://www.healthofchildren.com/N-O/Nail-Patella-Syndrome.html
Nail-patella syndrome has been recognized as an inherited disorder for over a hundred years. […] It is caused by mutations in a gene known as LIM Homeobox Transcription Factor 1-Beta (LMX1B), located on the long arm of chromosome 9. […] Mutations in this gene have been detected in many unrelated people with nail-patella syndrome. […] Nail-patella syndrome is inherited in an autosomal dominant manner. […] A new mutation causing nail-patella syndrome can also occur, causing disease in a child with no family history of the syndrome. […] This is called a sporadic occurrence and accounts for approximately 20 percent of cases of nail-patella syndrome.
#24
https://111.wales.nhs.uk/nailpatellasyndrome/
Nail patella syndrome is usually caused by a fault in a gene called LMX1B that’s inherited from one parent. […] But there isn’t always a family history of nail patella syndrome. In some cases, an LMX1B gene mutation (alteration) occurs for the first time on its own.
#25 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#26 Nail-Patella Syndrome – MD Searchlight
https://mdsearchlight.com/genetic-disorders/nail-patella-syndrome/
Nail-patella syndrome is an inherited disorder that is passed from parents to children. It is caused by a mutation in a specific gene called LMXB1, which resides on a particular section of chromosome 9. The LMXB1 gene is responsible for creating a protein that plays a critical role in the development of numerous body parts during embryonic stages, including certain parts of limbs, types of brain cells, skull structure, development around the eyes, and specific kidney cells. […] It is known that at least 142 types of changes or mutations in the LMXB1 gene can cause this syndrome. There is also evidence of what is known as somatic mosaicism, a condition where some cells have the genetic mutation causing the syndrome, while others do not. This often happens in parents who do not have the syndrome, but have a child who does.
#27 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#28 Nail-Patella Syndrome: Symptoms & Causes
https://my.clevelandclinic.org/health/diseases/nail-patella-syndrome
Nail-patella syndrome is a genetic condition that affects your child’s nails, bones, eyes and kidneys. It changes how these parts look and/or function. […] Changes to your child’s genes (gene variants) cause nail-patella syndrome. Most people with this syndrome have changes to their LMX1B gene. This gene tells your child’s body how to make a specific protein (LMX1B protein). This protein helps your child’s arms, legs, eyes and kidneys take shape during fetal development. […] Gene variants cause the LMX1B protein to work differently than expected. As a result, various parts of your child’s body don’t form in typical ways, leading to the features of nail-patella syndrome. […] Some people have the signs and symptoms of nail-patella syndrome without changes to their LMX1B gene. But this is rare. Researchers believe other genes might play a role, and they continue to look for more clues.
#29 NailâPatella Syndrome: clinical and molecular data in 55 families raising the hypothesis of a genetic heterogeneity | European Journal of Human Genetics
https://www.nature.com/articles/ejhg201577
NailPatella Syndrome (NPS) is due to variants affecting function in LMX1B, which encodes a LIM-homeodomain protein critical for limb, kidney and eye development. […] The main pathogenic mechanism underlying autosomal dominant NPS in humans is haploinsufficiency. […] The majority of patients carry either LMX1B variants or complete or partial deletions responsible for haploinsufficiency through the nonsense-mediated mRNA decay pathway. […] In the present study, we describe the phenotype and molecular data of 55 index patients and their 39 relatives affected with NPS. […] In 9% of families are not carriers of a LMX1B genomic alteration after extensive study of the coding and non-coding regions of the gene. […] One of the families showed no linkage to the LMX1B locus, raising the hypothesis of a genetic heterogeneity.
#30 NailâPatella Syndrome: clinical and molecular data in 55 families raising the hypothesis of a genetic heterogeneity | European Journal of Human Genetics
https://www.nature.com/articles/ejhg201577
In 9% of the families tested, no alteration was found in LMX1B by the routine screening. […] These variants have never been described. […] For family 51, segregation analysis was performed based on variants generated by next-generation sequencing and microsatellite markers. […] Interestingly, no linkage to LMX1B locus (9q33.3) was shown, suggesting that a genomic alteration of this gene is not involved for this particular family. […] To our knowledge, the hypothesis of a genetic heterogeneity has never been studied in NPS.
#31 Nail-Patella Syndrome: Symptoms & Causes
https://my.clevelandclinic.org/health/diseases/nail-patella-syndrome
Nail-patella syndrome is a genetic condition that affects your child’s nails, bones, eyes and kidneys. It changes how these parts look and/or function. […] Changes to your child’s genes (gene variants) cause nail-patella syndrome. Most people with this syndrome have changes to their LMX1B gene. This gene tells your child’s body how to make a specific protein (LMX1B protein). This protein helps your child’s arms, legs, eyes and kidneys take shape during fetal development. […] Gene variants cause the LMX1B protein to work differently than expected. As a result, various parts of your child’s body don’t form in typical ways, leading to the features of nail-patella syndrome. […] Some people have the signs and symptoms of nail-patella syndrome without changes to their LMX1B gene. But this is rare. Researchers believe other genes might play a role, and they continue to look for more clues.
#32 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#33 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#34 Nail-Patella Syndrome – MD Searchlight
https://mdsearchlight.com/genetic-disorders/nail-patella-syndrome/
Even though Nail-patella syndrome is likely to appear if the mutation is present, the symptoms can vary a great deal among different family members. This variability may be due to interactions that the LMXB1 gene has with other genes in the body. For example, the PAX2 gene, which also plays a role in kidney and eye development, may interact with the LMXB1 gene. If the LMXB1 gene is mutated, it may interact differently with the PAX2 gene, potentially influencing how Nail-patella syndrome presents. However, more research is needed to fully understand this potential interaction.
#35 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#36 Nail-Patella Syndrome | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/25513
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. […] At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#37 nail-patella syndrome
https://chromodisorder.org/cdo-news/nail-patella-syndrome/
Nail-patella syndrome is a disorder characterized by nail, skeletal, renal, and ocular abnormalities. Francis et al. present a family to support previous literature of how an atypical genetic etiology can yield more mild symptoms. […] Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by variable nail, skeletal, renal, and ocular abnormalities. The causative gene has been identified to be LMX1B, but not all families have showed clinically significant variants within this gene. […] Francis et al. identify a second family of 4 affected individuals with a separate, but overlapping LARM2 deletion, that segregates with clinical features of nail-patella syndrome, which further highlights how LARM2 deletions are responsible for a subset of unsolved NPS families. […] The authors also highlight how the three children could have renal symptoms emerge in adulthood; however, as it stands, this family supports previous literature that deletions of LARM2 yield more mild forms of NPS, further elucidating its variable expressivity.
#38 nail-patella syndrome
https://chromodisorder.org/cdo-news/nail-patella-syndrome/
Nail-patella syndrome is a disorder characterized by nail, skeletal, renal, and ocular abnormalities. Francis et al. present a family to support previous literature of how an atypical genetic etiology can yield more mild symptoms. […] Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by variable nail, skeletal, renal, and ocular abnormalities. The causative gene has been identified to be LMX1B, but not all families have showed clinically significant variants within this gene. […] Francis et al. identify a second family of 4 affected individuals with a separate, but overlapping LARM2 deletion, that segregates with clinical features of nail-patella syndrome, which further highlights how LARM2 deletions are responsible for a subset of unsolved NPS families. […] The authors also highlight how the three children could have renal symptoms emerge in adulthood; however, as it stands, this family supports previous literature that deletions of LARM2 yield more mild forms of NPS, further elucidating its variable expressivity.
#39 Nail patella syndrome: Causes, symptoms, treatment, inheritance
https://www.medicalnewstoday.com/articles/nail-patella-syndrome
NPS is an autosomal dominant genetic condition. […] Currently, the only known cause of NPS is a change, or mutation, in the LMX1B gene. Mutations in this gene cause changes and irregularities in the skeleton. […] However, about 10% of all new NPS cases occur as a spontaneous mutation when neither parent has the condition. […] There is no correlation between the specific mutation and the range and severity of the condition.
#40 Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02012-3
The diagnosis of NPS is associated with variable phenotypes, including nail changes present in 98% of the probands with the typical form of disease. […] Genetic analysis of LMX1B can be informative when a clinical diagnosis is uncertain or for individuals with atypical forms of NPS. […] However, clear genotype-phenotype correlation does not exist. […] The renal biopsy of individuals with NPLRD are heterogeneous and may show minimal-change disease, normal EM, effacement of podocyte foot processes, or a FSGS lesion. […] The FSGS lesion in our patient is consistent with what has been reported in association with the identified LMX1B variant. […] Thus, at this time it is not possible to establish a definite association between LMX1B, myeloid bodies and lyso-GB3 excretion, or if the deposition is secondary to lysosomal enzymatic deficiencies due to medications or infections. […] Together, these cases indicate that LMX1B-related diseases should be considered in the differential diagnosis of patient with renal biopsy showing myeloid bodies on EM.
#41 Nail-Patella Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK559190/
Nail-patella syndrome is an autosomal dominant disorder due to a heterozygous loss of function mutation of the LMXB1 gene on chromosome 9q34.1. LMXB1 encodes a transcription factor involved in multiple important embryological developments to include limb dorsal-ventral patterning, differentiation of dopaminergic and serotonergic neurons, skull patterning, periocular mesenchyme development, and renal podocyte development. At least 142 LMXB1 mutations have been identified as well as evidence of somatic mosaicism, which is known to occur in unaffected parents of patients affected by autosomal dominant disorders. NPS is highly penetrant, but there is inter- and intrafamilial variability contributing to the conditions variable clinical manifestations. […] Another factor contributing to the conditions various manifestations may include interactions between the LMXB1 homeodomain with other genes. The PAX2 transcription factor has been studied for its interaction with LMXB1 as both proteins are involved in renal and eye development. Mutations of the LMXB1 gene homeodomain have been shown to affect interactions with PAX2 raising the question of the latters role in the NPS phenotypic variability, although more research would be needed to test this possibility.
#42 Nail Patella Syndrome: Understanding Symptoms, Causes, and Management â¢ Yesil Health
https://yesilhealth.com/your-health/nail-patella-syndrome-understanding-symptoms-causes-and-management/
While genetic mutations are the primary cause, some researchers suggest that environmental factors may also play a role in the severity of symptoms. Factors such as nutrition, exposure to toxins, and overall health during pregnancy could potentially influence the expression of the syndrome. However, more research is needed to fully understand these interactions.
#43 Nail Patella Syndrome: Symptoms, Causes, Treatment!
https://www.lybrate.com/topic/nail-patella-syndrome
Nail Patella Syndrome is a genetic disorder that affects the natural structure of human nails, joints, nervous system, and kidneys. […] A genetic mutation in the LMX1B gene is the cause of the disorder. […] The development of Nail Patella Syndrome in a person is caused by a mutation in the LMX1B gene. Such a mutation is autosomal dominant in nature.
#44 Nailâpatella syndrome – Wikipedia
https://en.wikipedia.org/wiki/Nail%E2%80%93patella_syndrome
Causes mutations in the LMX1B gene. […] Nailpatella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9’s q arm (the longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for the disorder to be expressed in the offspring, meaning the chance of getting the disorder from an affected heterozygous parent is 50%. The frequency of the occurrence is 1/50,000. The disorder is linked to the ABO blood group locus. […] It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified. […] The lack of development or complete absence of fingernails results from the loss of function mutations in the LMX1B gene. This mutation may cause a reduction in dorsalising signals, which then results in the failure to normally develop dorsal specific structures such as nails and patellae.
#45 Nail-patella syndrome – wikidoc
https://www.wikidoc.org/index.php/Nail-patella_syndrome
Nail-patella syndrome is inherited in an autosomal dominant pattern. […] The Nail-Patella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9’s q arm (q stands for longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for disorder to be expressed in the offspring, meaning that the chance of getting the disorder from an affected parent is 50%. […] The disorder is linked to the ABO blood group locus.
#46 Nail-patella-syndrome in a young patient followed up over 10 years: relevance of the sagittal trochlear septum for patellofemoral pathology | SICOT-JMendeley
https://www.sicot-j.org/articles/sicotj/full_html/2016/01/sicotj150179/sicotj150179.html
Nail-patella-syndrome (NPS) is a rare autosomal-dominant inherited disease with pathologies of nails, skeleton, kidneys, and eyes. Linkage to a mutated gene was found. It codes for the transcription-factor LMX1B. In most cases knees are symptomatic. Patients have hypoplastic patellae, which are laterally subluxated. In those individuals a sagittal trochlear fibrous septum was found, dividing the anterior knee-joint-space. In the literature the etiology and clinical significance of this anatomic abnormality is unclear. […] The syndrome was mentioned first by Chaterlain in 1820. Linkage to a mutated gene was found. It is located on the long arm of chromosome nine in region 9q34, close to an AB0 blood group gene. It codes for the transcription factor LMX1B. Loss-of-function mutations of LMX1B cause NPS.
#47
https://www.omim.org/entry/161200
A number sign (#) is used with this entry because of evidence that nail-patella syndrome (NPS) is caused by heterozygous mutation in the LIM-homeodomain protein LMX1B (602575) on chromosome 9q33. […] Heterozygous mutation in the LMX1B gene can also cause isolated nephropathy, known as FSGS10 (256020). […] The heterozygous mutations in the LMX1B gene that were identified in patients with NPS by Dreyer et al. (1998) occurred de novo. […] The transmission pattern of NPS in the families reported by Vollrath et al. (1998) was consistent with autosomal dominant inheritance. […] Ghiggeri et al. (1993) suggested that mutations in the COL5A1 gene may be involved in the pathogenesis of the nail-patella syndrome. […] Duba et al. (1998) suggested that the translocation may aid in the identification of the gene.
#48 Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02012-3
Genetic changes in the LIM homeobox transcription factor 1 beta (LMX1B) have been associated with focal segmental glomerulosclerosis (FSGS) without the extra-renal or ultrastructural manifestations of Nail-patella syndrome (NPS) known as Nail-patella-like renal disease (NPLRD). […] Nail-patella syndrome (NPS; OMIM #161200) is an autosomal dominant disease caused by variants in LMX1B which encodes for the LIM homeobox transcription factor 1 beta that plays a critical role in the development of the limb structures, glomerular basement membrane in the eye, kidney, and neurons. […] However some individuals may present with renal involvement without skeletal or extrarenal manifestations, a condition known as Nail-patella-like renal disease (NPLRD) or LMX1B-associated nephropathy (OMIM #256020).
#49 Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02012-3
Genetic changes in the LIM homeobox transcription factor 1 beta (LMX1B) have been associated with focal segmental glomerulosclerosis (FSGS) without the extra-renal or ultrastructural manifestations of Nail-patella syndrome (NPS) known as Nail-patella-like renal disease (NPLRD). […] Nail-patella syndrome (NPS; OMIM #161200) is an autosomal dominant disease caused by variants in LMX1B which encodes for the LIM homeobox transcription factor 1 beta that plays a critical role in the development of the limb structures, glomerular basement membrane in the eye, kidney, and neurons. […] However some individuals may present with renal involvement without skeletal or extrarenal manifestations, a condition known as Nail-patella-like renal disease (NPLRD) or LMX1B-associated nephropathy (OMIM #256020).
#50 Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02012-3
The diagnosis of NPS is associated with variable phenotypes, including nail changes present in 98% of the probands with the typical form of disease. […] Genetic analysis of LMX1B can be informative when a clinical diagnosis is uncertain or for individuals with atypical forms of NPS. […] However, clear genotype-phenotype correlation does not exist. […] The renal biopsy of individuals with NPLRD are heterogeneous and may show minimal-change disease, normal EM, effacement of podocyte foot processes, or a FSGS lesion. […] The FSGS lesion in our patient is consistent with what has been reported in association with the identified LMX1B variant. […] Thus, at this time it is not possible to establish a definite association between LMX1B, myeloid bodies and lyso-GB3 excretion, or if the deposition is secondary to lysosomal enzymatic deficiencies due to medications or infections. […] Together, these cases indicate that LMX1B-related diseases should be considered in the differential diagnosis of patient with renal biopsy showing myeloid bodies on EM.
#51 Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02012-3
The diagnosis of NPS is associated with variable phenotypes, including nail changes present in 98% of the probands with the typical form of disease. […] Genetic analysis of LMX1B can be informative when a clinical diagnosis is uncertain or for individuals with atypical forms of NPS. […] However, clear genotype-phenotype correlation does not exist. […] The renal biopsy of individuals with NPLRD are heterogeneous and may show minimal-change disease, normal EM, effacement of podocyte foot processes, or a FSGS lesion. […] The FSGS lesion in our patient is consistent with what has been reported in association with the identified LMX1B variant. […] Thus, at this time it is not possible to establish a definite association between LMX1B, myeloid bodies and lyso-GB3 excretion, or if the deposition is secondary to lysosomal enzymatic deficiencies due to medications or infections. […] Together, these cases indicate that LMX1B-related diseases should be considered in the differential diagnosis of patient with renal biopsy showing myeloid bodies on EM.
#52 Nail Patella Syndrome | International Center for Limb Lengthening
https://www.limblength.org/conditions/nail-patella-syndrome/
Nail patella syndrome, also referred to as NPS, Turner-Kieser syndrome, or hereditary onychoosteodysplasia (HOOD) is a rare genetic disorder affecting the proper development of the fingernails/toenails, kneecap (patella), elbow and/or hip bone. […] The most common cause of nail patella syndrome is a mutation of the LMX1B (LIM homeobox transcription factor 1 beta) gene that controls the development of our skeletal system, particularly the parts of the body mentioned above. This mutation is passed down from parents to children in an autosomal dominant inheritance, meaning there is a 50% chance an affected parent will pass nail patella syndrome onto their offspring.
#53 Nail-patella syndrome | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/nail-patella-syndrome?lang=us
Nail-patella syndrome, also known as Fong disease, is a rare autosomal dominant condition which results from symmetrical mesodermal and ectodermal abnormalities. […] The underlying genetic defect is caused by loss-of-function mutations in the transcription factor LMX1B on chromosome 9.
#54 Nail Patella Syndrome – THC Doctors
https://www.thc-doctors.com/nail-patella-syndrome/
Nail patella syndrome (NPS) is a genetic disorder that results in small, poorly developed nails and kneecaps, but can also affect many other areas of the body, such as the elbows, chest, and hips. […] The name nail-patella can be very misleading because the syndrome often affects many other areas of the body, including even the production of certain proteins. […] It is also referred to as iliac horn syndrome, hereditary onychoostedysplasia, Fong disease or Turner Kiser syndrome. […] The hallmark features of this syndrome are poorly developed fingernails, toenails, and patellae (kneecaps). […] Other common abnormalities include elbow deformities, abnormally shaped pelvic (hip) bones, and kidney (renal) disease. […] Also, some research shows people with NPS are more prone to glaucoma and scoliosis, due to poorly developed spines.
#55 Nail-Patella Syndrome | Consultant360
https://www.consultant360.com/content/nail-patella-syndrome
The classic clinical tetrad of nail-patella syndrome (also known as Fong disease, Turner syndrome, and hereditary onycho-osteodysplasia) involves the nails, knees, and elbows, and the presence of iliac horns. This autosomal dominant condition is associated with the LMX1B gene on chromosome 9 (9q34). The incidence is roughly estimated at 1 in 50,000. The syndrome has been reported in a variety of ethnic groups. […] Nail-patella syndrome is associated with hypothyroidism, irritable bowel syndrome, attention deficit hyperactivity disorder, and thin tooth enamel. The precise nature of these associations remains unclear.
#56 Gene Responsible For Nail-Patella Syndrome Found | ScienceDaily
https://www.sciencedaily.com/releases/1998/04/980429123420.htm
The gene responsible for a rare condition causing abnormal fingernails and the lack of kneecaps has been identified by researchers at Baylor College of Medicine and the M.D. Anderson Cancer Center, Houston. Mutations in LMX1B can cause nail-patella syndrome, which can also result in glaucoma and kidney failure.
#57
https://www.omim.org/entry/161200
The LIM-homeodomain protein Lmx1b plays a central role in dorsal/ventral patterning of the vertebrate limb. Targeted disruption of Lmx1b results in skeletal defects, including hypoplastic nails, absent patellae, and a unique form of renal dysplasia (Chen et al., 1998). […] Dreyer et al. (1998) showed that the LMX1B gene maps to 9q in the same region as the NPS locus by fluorescence in situ hybridization. Furthermore, they demonstrated that 3 unrelated NPS patients carried de novo heterozygous mutations in this gene. […] These were the first described mutations in a LIM-homeodomain protein that accounted for an inherited form of abnormal skeletal patterning and renal failure. […] Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene (602575.0013) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome.
#58
https://www.omim.org/entry/161200
The LIM-homeodomain protein Lmx1b plays a central role in dorsal/ventral patterning of the vertebrate limb. Targeted disruption of Lmx1b results in skeletal defects, including hypoplastic nails, absent patellae, and a unique form of renal dysplasia (Chen et al., 1998). […] Dreyer et al. (1998) showed that the LMX1B gene maps to 9q in the same region as the NPS locus by fluorescence in situ hybridization. Furthermore, they demonstrated that 3 unrelated NPS patients carried de novo heterozygous mutations in this gene. […] These were the first described mutations in a LIM-homeodomain protein that accounted for an inherited form of abnormal skeletal patterning and renal failure. […] Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene (602575.0013) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome.
#59
https://www.omim.org/entry/161200
The LIM-homeodomain protein Lmx1b plays a central role in dorsal/ventral patterning of the vertebrate limb. Targeted disruption of Lmx1b results in skeletal defects, including hypoplastic nails, absent patellae, and a unique form of renal dysplasia (Chen et al., 1998). […] Dreyer et al. (1998) showed that the LMX1B gene maps to 9q in the same region as the NPS locus by fluorescence in situ hybridization. Furthermore, they demonstrated that 3 unrelated NPS patients carried de novo heterozygous mutations in this gene. […] These were the first described mutations in a LIM-homeodomain protein that accounted for an inherited form of abnormal skeletal patterning and renal failure. […] Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene (602575.0013) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome.
#60 A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression | European Journal of Human Genetics
https://www.nature.com/articles/5201332
Nail patella syndrome (NPS) is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. […] The neurological problems may be related to abnormalities of the dorsal-ventral patterning of the developing limb including abnormal neuronal migration. […] Alternatively, the neurological symptoms may result from a primary dysfunction of LMX1B within the sensory circuit. […] A pathophysiological mechanism linking Lmx1b expression to a neurological phenotype in NPS is proposed. […] The pattern of lmx1b expression observed in limb, eye and kidney correlates with the recognized signs and symptoms of NPS. […] The degree of impairment may be correlated with age since the mildest symptoms were seen in adolescents, and two of the highest scores in subjects over 50 years, but a larger (preferably longitudinal) study is required to address this issue. […] Therefore, in individuals with NPS, deficient A and C fiber projection into laminae I and II may be associated with the neuropathic pain, tingling, and impaired pinprick and cold sensations observed in this study.
#61 A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression | European Journal of Human Genetics
https://www.nature.com/articles/5201332
Nail patella syndrome (NPS) is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. […] The neurological problems may be related to abnormalities of the dorsal-ventral patterning of the developing limb including abnormal neuronal migration. […] Alternatively, the neurological symptoms may result from a primary dysfunction of LMX1B within the sensory circuit. […] A pathophysiological mechanism linking Lmx1b expression to a neurological phenotype in NPS is proposed. […] The pattern of lmx1b expression observed in limb, eye and kidney correlates with the recognized signs and symptoms of NPS. […] The degree of impairment may be correlated with age since the mildest symptoms were seen in adolescents, and two of the highest scores in subjects over 50 years, but a larger (preferably longitudinal) study is required to address this issue. […] Therefore, in individuals with NPS, deficient A and C fiber projection into laminae I and II may be associated with the neuropathic pain, tingling, and impaired pinprick and cold sensations observed in this study.
#62 A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression | European Journal of Human Genetics
https://www.nature.com/articles/5201332
Nail patella syndrome (NPS) is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. […] The neurological problems may be related to abnormalities of the dorsal-ventral patterning of the developing limb including abnormal neuronal migration. […] Alternatively, the neurological symptoms may result from a primary dysfunction of LMX1B within the sensory circuit. […] A pathophysiological mechanism linking Lmx1b expression to a neurological phenotype in NPS is proposed. […] The pattern of lmx1b expression observed in limb, eye and kidney correlates with the recognized signs and symptoms of NPS. […] The degree of impairment may be correlated with age since the mildest symptoms were seen in adolescents, and two of the highest scores in subjects over 50 years, but a larger (preferably longitudinal) study is required to address this issue. […] Therefore, in individuals with NPS, deficient A and C fiber projection into laminae I and II may be associated with the neuropathic pain, tingling, and impaired pinprick and cold sensations observed in this study.
#63 A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression | European Journal of Human Genetics
https://www.nature.com/articles/5201332
Nail patella syndrome (NPS) is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. […] The neurological problems may be related to abnormalities of the dorsal-ventral patterning of the developing limb including abnormal neuronal migration. […] Alternatively, the neurological symptoms may result from a primary dysfunction of LMX1B within the sensory circuit. […] A pathophysiological mechanism linking Lmx1b expression to a neurological phenotype in NPS is proposed. […] The pattern of lmx1b expression observed in limb, eye and kidney correlates with the recognized signs and symptoms of NPS. […] The degree of impairment may be correlated with age since the mildest symptoms were seen in adolescents, and two of the highest scores in subjects over 50 years, but a larger (preferably longitudinal) study is required to address this issue. […] Therefore, in individuals with NPS, deficient A and C fiber projection into laminae I and II may be associated with the neuropathic pain, tingling, and impaired pinprick and cold sensations observed in this study.
#64 Orphanet: Nail-patella syndrome
https://www.orpha.net/en/disease/detail/2614
A rare hereditary patellar dysostosis characterized by nail hypoplasia or aplasia, aplastic or hypoplastic patellae, elbow dysplasia, and the presence of iliac horns as well as renal and ocular anomalies. […] NPS is an autosomal-dominant disorder and the majority of the cases are caused by LMX1B mutations (9q33.3) leading to loss of function of the LMX1B protein. About 10% are caused by a de novo pathogenic variant.
#65 Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02012-3
The diagnosis of NPS is associated with variable phenotypes, including nail changes present in 98% of the probands with the typical form of disease. […] Genetic analysis of LMX1B can be informative when a clinical diagnosis is uncertain or for individuals with atypical forms of NPS. […] However, clear genotype-phenotype correlation does not exist. […] The renal biopsy of individuals with NPLRD are heterogeneous and may show minimal-change disease, normal EM, effacement of podocyte foot processes, or a FSGS lesion. […] The FSGS lesion in our patient is consistent with what has been reported in association with the identified LMX1B variant. […] Thus, at this time it is not possible to establish a definite association between LMX1B, myeloid bodies and lyso-GB3 excretion, or if the deposition is secondary to lysosomal enzymatic deficiencies due to medications or infections. […] Together, these cases indicate that LMX1B-related diseases should be considered in the differential diagnosis of patient with renal biopsy showing myeloid bodies on EM.
#66 Nail-patella syndrome | qualifyingconditions
https://www.qualifyingconditions.com/copy-of-muscle-spasms-severe
Nail-patella syndrome (NPS) is a genetic disorder that causes abnormalities in the nails, and sometimes the knees, elbows and pelvis. […] NPS is related to mutations in the LMX1B gene. The mutation is primarily inherited from one affected parent, however, in rare cases, the syndrome develops in people that dont have the history of the disorder in their family. […] Imaging tests may allow NPS to be detected prenatally in some cases. Other cases may not be diagnosed until birth or early childhood when nail and other related abnormalities develop.
#67 Rare Disease Education: Nail-Patella Syndrome
https://prod.sdgresources.relx.com/features/rare-disease-education-nail-patella-syndrome
Just as coin flip has a 50% chance of falling on heads, so too is the chance of transmission of Nail-Patella Syndrome from parent to child. […] Nail-Patella Syndrome is a genetic disorder that affects approximately one in 50 thousand people and typically runs in families with 90% of people with this Zebra having an affected parent. […] When suspected, genetic testing for LMX1B mutations confirms the diagnosis.