Materiały źródłowe

• #1 Turner syndrome: mechanisms and management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/31213699/

  Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. […] Turner syndrome is associated with short stature, delayed puberty, ovarian dysgenesis, hypergonadotropic hypogonadism, infertility, congenital malformations of the heart, endocrine disorders such as type 1 and type 2 diabetes mellitus, osteoporosis and autoimmune disorders. […] Here, we present an updated Review of Turner syndrome, covering advances in genetic and genomic mechanisms of disease, associated disorders and multidisciplinary approaches to patient management, including growth hormone therapy and hormone replacement therapy.

• #2 Turner Syndrome

  https://www.mdpi.com/2673-396X/3/2/22

  Turner syndrome (TS) affects approximately 1 out of every 1500–2500 live female births, with clinical features including short stature, premature ovarian failure, dysmorphic features and other endocrine, skeletal, cardiovascular, renal, gastrointestinal and neurodevelopmental organ system involvement. TS, a common genetic syndrome, is caused by sex chromosome aneuploidy, mosaicism or abnormalities with complete or partial loss of function of the second X chromosome. […] Advances in genetic and genomic testing have further elucidated other possible mechanisms that contribute to pathogenic variability in phenotypic expression that are not necessarily explained by monosomy or haploinsufficiency of the X chromosome alone. The role of epigenetics in variations of gene expression and how this knowledge can contribute to more individualized therapy is currently being explored.

• #3 Turner Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554621/

  Turner syndrome results from a deletion or the non-functioning of one X chromosome in females. About half of the population with Turner syndrome have monosomy X (45,XO). The other 50% of the population has a mosaic chromosomal component (45,X with mosaicism). […] Most instances of Turner syndrome are not inherited. When monosomy X is the cause, the chromosomal abnormality is a random event during the formation of reproductive cells in the persons parent. An error in cell division is called nondisjunction and can result in reproductive cells with an abnormal number of chromosomes. For example, a sex chromosome can become lost from an egg or a sperm cell due to nondisjunction. If an atypical reproductive cell contributes to the genetic makeup of a child, each cell will possess a single X chromosome, and the other sex chromosome will be missing.

• #4 Turner syndrome: mechanisms and management | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-019-0224-4

  Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. […] Here, we present an updated Review of Turner syndrome, covering advances in genetic and genomic mechanisms of disease, associated disorders and multidisciplinary approaches to patient management, including growth hormone therapy and hormone replacement therapy. […] Turner syndrome is a rare disorder caused by a completely or partially missing X chromosome; diagnosis of this condition is often delayed. […] Most women with Turner syndrome experience primary or secondary hypergonadotropic hypogonadism, which necessitates treatment with hormone replacement therapy. […] Compared with the general population, morbidity and mortality are increased in women with Turner syndrome owing to a broad swathe of diseases, demanding vigilance as the individual ages. […] Optimal care for Turner syndrome necessitates a multidisciplinary team optimally situated within the framework of one hospital.

• #5 Turner Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/15200-turner-syndrome

  Turner syndrome (TS) is a congenital condition (present from birth) that only affects females. It happens when one of two of the X chromosomes is missing, either partially or completely. […] Turner syndrome happens when one of a baby’s two X chromosomes is missing or incomplete. Researchers don’t yet understand why this happens. […] There are different types of Turner syndrome (TS) based on how one of the X chromosomes is affected: Monosomy X: This type means each cell has only one X chromosome instead of two. About 45% of people with TS have monosomy X. The chromosomal abnormality happens randomly during the formation of reproductive cells (eggs or sperm) in the affected person’s biological parent. If one of these atypical reproductive cells contributes to the genetic makeup of a fetus during conception, the baby will have a single X chromosome in each cell at birth.

• #6 Turner Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/15200-turner-syndrome

  Mosaic Turner syndrome: This type makes up about 30% of TS cases. Some of your child’s cells have a pair of X chromosomes, while other cells only have one. It happens randomly during cell division early in pregnancy. […] Inherited Turner syndrome: In rare cases, babies may have inherited TS, meaning their biological parent was born with it and passed it on. This type usually happens because of a missing part of the X chromosome.

• #7 Turner Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/949681-overview

  Turner syndrome is caused by the absence of one set of genes from the short arm of one X chromosome. […] Turner syndrome is caused by the absence of one set of genes from the short arm of one X chromosome. In patients with 45,X karyotype, about two thirds are missing the paternal X chromosome. In addition to monosomy X, a similar clinical picture is found with a 46,XXiq karyotype and in some individuals with mosaic karyotypes. A deletion of the SHOX gene can cause a similar skeletal phenotype known as Leri-Weill dyschondrosteosis.

• #8 Turner Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554621/

  Turner syndrome results from a deletion or the non-functioning of one X chromosome in females. About half of the population with Turner syndrome have monosomy X (45,XO). The other 50% of the population has a mosaic chromosomal component (45,X with mosaicism). […] Most instances of Turner syndrome are not inherited. When monosomy X is the cause, the chromosomal abnormality is a random event during the formation of reproductive cells in the persons parent. An error in cell division is called nondisjunction and can result in reproductive cells with an abnormal number of chromosomes. For example, a sex chromosome can become lost from an egg or a sperm cell due to nondisjunction. If an atypical reproductive cell contributes to the genetic makeup of a child, each cell will possess a single X chromosome, and the other sex chromosome will be missing.

• #9

  https://byjus.com/neet/what-is-turner-syndrome/

  Turner syndrome is a genetic condition related to the X chromosome. The total chromosome number in Turner syndrome becomes 45 chromosomes instead of the normal 46 chromosomes. In this condition, the female either partially or completely misses an X chromosome. […] Turner syndrome is a genetic disorder. It is due to aneuploidy of the sex chromosome. One X chromosome is missing in all the cells or some cells. Only females are born with this condition. […] The turner syndrome can be due to many reasons […] Monosomy of X: This accounts for half of the Turner syndrome cases. There is a complete loss of one X chromosome. This results from the abnormal cell division during gamete formation. Eggs or sperm lack a sex chromosome. […] Mosaicism: When the sex chromosome is lost during mitosis after fertilisation, i.e. during the development of the zygote, it results in some cells with 45 chromosomes (one X chromosome) and some cells having normal 46 chromosomes (XX chromosomes).

• #10 Laboratory guideline for Turner syndrome | Genetics in Medicine

  https://www.nature.com/articles/gim20108

  The features of Turner syndrome include characteristic physical features and complete or partial absence of the second sex chromosome. […] Turner syndrome is sporadic. A majority of cases ascertained prenatally have a 45,X karyotype. Paternal nondisjunction accounts for 70% of liveborn cases with a 45,X. […] A differential diagnosis that includes Turner syndrome must take into consideration phenotypic features in combination with karyotypic findings. […] Mosaicism for a cell line with a normal or abnormal Y chromosome is identified in 6% to 11% of patients with Turner syndrome with standard cytogenetic techniques. […] Identification of Y chromosome material in females with Turner syndrome is important because of the risk of gonadoblastoma. […] The neoplasm does not appear to correlate with the presence of SRY.

• #11 Turner Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554621/

  Mosaic Turner syndrome is likewise not an inherited condition. It occurs due to a random event during the cell division stage in the early fetal development of the affected individual. As a result, some of a person’s cells have the usual two sex chromosomes, while other cells contain only one copy of the X chromosome. Other sex chromosome abnormalities are possible in females with X chromosome mosaicism. Rarely, Turner syndrome can result from a partial deletion of the X chromosome, and this can pass from one generation to the next.

• #12 Mosaic Turner Syndrome: What It Is and How It’s Treated

  https://www.healthline.com/health/childrens-health/mosaic-turner-syndrome

  Turner syndrome is a chromosomal condition involving a persons sex chromosomes. It is considered mosaic when an X chromosome is missing in some cells in people who have two X chromosomes. […] Turner syndrome results when one of the X chromosomes (sex chromosomes) is missing or partially missing following conception. […] In mosaic Turner syndrome, an X chromosome is missing in some cells in people assigned female at birth. […] The mosaic form of this condition is caused by a partial loss of the second X chromosome. The one-chromosome form is caused by a complete loss of the second X chromosome. […] What causes the loss of this second sex chromosome isnt fully understood yet. Researchers believe it may happen at random during reproduction. It could occur soon after the sperm meets the egg or early in fetal development.

• #13 Epigenetics in Turner syndrome | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0477-0

  Turner syndrome is due to a partial or total loss of the second sexual chromosome, resulting in the development of highly variable clinical features. […] This phenotype may not merely be due to genomic imbalance from deleted genes but may also result from additive influences on associated genes within a given gene network, with an altered regulation of gene expression triggered by the absence of the second sex chromosome. […] Current studies in human and mouse models have demonstrated that this chromosomal abnormality leads to epigenetic changes, including differential DNA methylation in specific groups of downstream target genes in pathways associated with several clinical and metabolic features, mostly on autosomal chromosomes. […] The clarification of these possible causal pathways may have future implications in increasing the life expectancy of these patients and may provide informative targets for early pharmaceutical intervention.

• #14 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  Humans have 46 chromosomes. Chromosomes contain all of your genes and DNA, the building blocks of the body. Two of these chromosomes, the sex chromosomes, determine if you become a boy or a girl. Loss the paternally or maternally derived X chromosome would lead to the class 45 XO karyotype. Sometimes, an individual may have two cells lines with different genetic makeups. The percentage of this mosaicism is said to determine the severity of the phenotype in the patient. Structural abnormalities such as the formation of a ring chromosome or an isochromosome and other mechanisms such as lyonization or imprinting also play a role in the pathophysiology of Turner Syndrome. […] Turner syndrome is not an inherited condition. […] Therefore the physical manifestations of Turners syndrome are due to aneuploidy, absence of two normal sex chromosomes or haploinsufficiency (presence of 1 set of genes in the cell instead of 2 ) of genes present in the Y chromosome.

• #15 Clinical and genetic aspects of Turner’s syndrome | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-clinical-genetic-aspects-turner39s-syndrome-S1665579616300503

  Turner’s syndrome, or monosomy X, is defined as the total or partial loss of the second sex chromosome. The clinical phenotype is highly variable and includes short stature, gonadal dysgenesis, pterygium colli, cubitus valgus and low hairline. […] Understanding its complex etiology and learning more about its clinical variability and complications will allow us to advance the therapeutic and management approach of such patients. […] The variable expressivity of height and other physical features may be only partially related to the chromosomal formula, even when most recent studies do not show a clear genotype-phenotype correlation. […] The Turner’s syndrome phenotype can be explained by a haploinsufficiency of the genes which are normally expressed in both sexual chromosomes and which escape X inactivation.

• #16 The role of the SHOX gene in the pathophysiology of Turner syndrome | Endocrinología y Nutrición (English Edition)

  https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-the-role-shox-gene-in-S2173509311000286

  Turner syndrome (TS) affects 1:2500 live females. It is caused by partial or complete absence of a sex chromosome. Patients with deletions of the distal segment of the short arm of X chromosome (Xp-) including haploinsufficiency of the SHOX (short stature homeobox) have, more often, short stature, skeletal abnormalities and hearing impairments. This article evaluates the current knowledge of the SHOX gene role in TS pathophysiology. […] Genetic anomaly is determined by the absence of genes on X chromosome. That is, the TS phenotype can be determined by a haploinsufficiency of genes bound to the X chromosome that escapes inactivation. Although one X chromosome undergoes inactivation in normal females during early embryogenesis, about 15% of all X chromosome genes, mostly situated on the short arm (Xp), remain active to some degree on both X chromosomes.

• #17 Turner Syndrome | Oncohema Key

  https://oncohemakey.com/turner-syndrome-2/

  Besides an error in meiosis, the other possibility explaining monosomy X is a postzygotic nonsegregation in mitosis. […] In addition to nonsegregation in meiosis and mitosis, there are a number of structural anomalies of the X chromosome, including isochromosome X and partial deletion of Xp and Xq. […] The X isochromosome is the most common isochromosome in humans, and it is likely caused by chromosome breakage and recombination in the proximal Xp, resulting in an isodicentric X i(Xq) chromosome. […] The compensation mechanism is X chromosome inactivation (XCI), which is achieved by the ribonucleic acid (RNA) coding gene XIST expressed on the inactive X chromosome; XIST then coats the inactive X chromosome making it inactive. […] However, 20% to 30% of X-linked genes escape X inactivation and are expressed on the inactive X chromosome.

• #18 About Turner Syndrome

  http://www.genome.gov/Genetic-Disorders/Turner-Syndrome

  Turner syndrome is a chromosomal condition related to the X chromosome. […] Researchers have not yet determined which genes on the X chromosome are responsible for most signs and symptoms of Turner syndrome. They have, however, identified one gene called SHOX that is important for bone development and growth. Missing one copy of this gene likely causes short stature and skeletal abnormalities in women with Turner syndrome. […] Turner syndrome occurs when one of the two X chromosomes normally found in women is missing or incomplete. Although the exact cause of Turner syndrome is not known, it appears to occur as a result of a random error during the formation of either the eggs or sperm. […] In Turner syndrome, the girl does not have the usual pair of two complete X chromosomes. The most common scenario is that the girl has only one X chromosome in her cells. Some girls with Turner syndrome do have two X chromosomes, but one of the X chromosomes is incomplete. In another scenario, the girl has some cells in her body with two X chromosomes, but other cells have only one. This is called mosaicism.

• #19 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  A study of 67 Turner syndrome in China found 50 percent of the patients with the classic 45 X karyotype followed by the mosaic pattern, a chromosomal structural abnormality (isochromosome or ring chromosome) and a Y chromosomal structural abnormality. […] Turner syndrome might be due to the partial or complete absence of these inactivated genes and the presence of functional homologues of the Y chromosome. […] Short Stature is said to be due to the haploinsufficiency of the short stature homeobox (SHOX gene) which is located on the pseudoautosomal region of the X chromosome. […] The SHOX gene is also responsible for skeletal abnormalities such as high arched palate, abnormal auricular development, cubitus valgus, genu valgum, Madelung deformity and short metacarpals. […] Premature ovarian failure is secondary to ovarian dysgenesis and early follicular apoptosis.

• #20 Turner Syndrome where are we? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03337-0

  Turner syndrome (TS) results from the loss of one X chromosome in phenotypic females, leading to a range of complications such as short stature, cardiovascular issues, autoimmune disorders, metabolic imbalances, osteoporosis, neurocognitive deficits, hearing loss, abnormalities in endocrine functions, infertility, disruptions in bone metabolism, and neurocognitive deficits. […] Turner Syndromes phenotype and genotype correlations are generally poor, and the exact cause remains incompletely understood. However, it is believed to result from both genomic imbalances induced by sex chromosome genes and the additive effect of epigenetic factors on linked genes within gene networks. […] The short stature homeobox-containing gene (SHOX) regulates growth, and its haploinsufficiency contributes to the characteristic short stature in TS.

• #21 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  The frequency of Xp deletion in patients with TS is approximately 2%. Short stature, gonadal dysgenesis and characteristic TS stigmatas are especially observed in patients who show deletion of the entire short arm. Furthermore, the phenotype is variable in partial deletions. […] The region Xp22.33-Xp22.12 contains the SHOX gene, which is located in the terminal region. The gene escapes from X inactivation, and its function is dosage dependent. Therefore, haplo-insufficiency of SHOX gene causes growth retardation. The SHOX gene is expressed in the pharyngeal arch, limbs, osteogenic cells, bone marrow, and fibroblasts. As well as short stature, skeletal abnormalities including short metacarpals, high palate, cubitus valgus, Madelung deformity, and mesomelic dysplasia may also be seen in the haplo-insufficiency of the gene.

• #22 The role of the SHOX gene in the pathophysiology of Turner syndrome | Endocrinología y Nutrición (English Edition)

  https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-the-role-shox-gene-in-S2173509311000286

  Patients with TS and deletions at the end of the short arm of X-chromosome (Xp-), including haploinsufficiency of the SHOX gene (short stature homeobox), have short stature and orthopedic abnormalities (e.g.: cubitus valgus, Madelung deformity, micrognatia, and high-arched palate) and hearing impairment. […] Most TS individuals have only two copies of the SHOX gene. Nevertheless, the haploinsufficiency of the SHOX gene does not explain all the anomalies in TS, suggesting that other genes take part in this process. […] The linear growth of the TS is defective since intrauterine life and tends to decelerate by 5-7 years-old. The pubertal spurt is absent even in those girls with spontaneous pubertal development. These alterations make short stature (a 20cm deficit in the final height) one of the main features of Turner syndrome.

• #23 The role of the SHOX gene in the pathophysiology of Turner syndrome | Endocrinología y Nutrición (English Edition)

  https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-the-role-shox-gene-in-S2173509311000286

  The deficiency of the SHOX gene seems to be one of the main causes of short stature in patients with Leri-Weill syndrome (LWS), Langer mesomelic dysplasia and also of proportional short stature in patients with isolated short stature. […] The main skeletal abnormalities in TS, related to SHOX deletions are micrognatia, cubitus valgus, high-arched palate and short metacarpals and metatarsals. […] Up to now, SHOX expression was not detected in cardiac, renal or vascular organogenesis. This fact suggests that SHOX probably does not have a role in the development of non-skeletal somatic features in the Turner phenotype. […] The diseases of the middle ear start in childhood, being responsible for a morbidity parcel of these patients. Recurrent suppurative otitis media and cholesteatoma are the most common disorders. The hearing loss can be conductive, sensorineural or mixed, whose prevalence increases with age. […] The SHOX gene is related to a peculiar situation, where mutations affecting a single gene can cause multiple phenotypes. Thus, more studies are needed in order to increase the understanding of the function of this gene.

• #24 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  The cytogenetic studies have shown that the region between Xq13 and Xq28 is important for normal ovarian function. The Xq13-q21 region is defined as the critical region (CR) 1, and the proximal deletions of this region are usually compatible with normal menstruation and fertility. The terminal and interstitial deletions of the CR2 at Xq23-q28 are mostly responsible for premature ovarian failure. The FMR1 gene, which is important in the ovarian function, is localized in the Xq27.3 locus, and expansions in the exon 1 triplet repeat of the gene are associated with an increased risk of early menopause. […] Approximately 50% of TS patients have 45,X karyotype and the most common structural X chromosome abnormality is isochromosome Xq. The retained X chromosome is maternally derived in two thirds of the patients. The patients with 46,XY cell line mosaicism or structural rearrangement of the Y chromosome mostly have masculinized external genitalia and are at increased risk of developing gonadoblastoma and other gonadal tumors, whereas patients with mosaic 46,XX karyotype or isochromosome Xq have a milder phenotype.

• #25 Laboratory guideline for Turner syndrome | Genetics in Medicine

  https://www.nature.com/articles/gim20108

  Turner syndrome is a disorder that has distinct clinical features and has karyotypic aberrations with loss of critical regions of the X chromosome. […] A majority of genes associated with the physical features observed in Turner syndrome are located on Xp (Xp11.2-p22); loci contributing to ovarian function reside in Xq (Xq24). […] The disease incidence is approximately 1 in 2500 liveborn females. A 45,X karyotype is observed in 1% to 2% of conceptuses, 10% of miscarriages and 1% of stillbirths. Greater than 99% of 45,X conceptuses result in spontaneous loss, usually before 28 weeks. […] Apparently nonmosaic monosomy X is found in 45% of patients with Turner syndrome postnatally. A structural chromosome abnormality or mosaicism for 45,X and another cell line is found in the lymphocytes of the remaining patients with Turner syndrome.

• #26 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  Increased susceptibility to gonadoblastomas are seen in those individuals with Y chromosomal abnormality karyotypes. […] Presence of autoimmune diseases may be due to haploinsufficiency of X chromosome or due to proinflammatory cytokines such as IL-6, IL-8 and tumor necrosis factor alpha. […] While phenotype-karyotype correlations are unreliable in predicting clinical features in Turner syndrome, some studies have suggested the following: Loss of short and long arm of X chromosome decreased ovarian function, number and survival of oocytes. […] Loss of interstitial or terminal long arm of X chromosome Short stature, primary or secondary ovarian failure. […] Loss of a region at Xp22.3 Neurocognitive problems. […] Loss of a region at Xp11.4 Critical for the development of lymphedema. […] Presence of an isochromosome Xq Increased risk of hypothyroidism and inflammatory bowel disease. […] Presence of ring chromosome Increased risk of mental retardation. […] Lack of the XIST locus Phenotype with more severe mental retardation.

• #27 Turner Syndrome

  https://www.mdpi.com/2673-396X/3/2/22

  More recent data support the role of altered gene expression as a result of epigenetic mechanisms as contributory to the varied clinical manifestations of TS, and is further discussed in this review. […] However, phenotypic variability in TS cannot be explained by genomic imbalance alone. It is postulated that other processes such as X-chromosome inactivation and altered gene expression as a result of epigenetic factors are also contributory. […] The genes on the short arm of X chromosome which escape X-inactivation are implicated in the TS phenotype. […] The degree of haploinsufficiency involved in TS depends on the karyotype; the 45,X karyotype involves greater haploinsufficiency than mosaic karyotypes. […] An example of the contribution of haploinsufficiency associated with the skewed inactivation pattern resulting from Turner syndrome karyotype is with respect to the previously identified short stature homeobox, or SHOX gene, which is located on Xp22.23, and thus far is the only gene that has been compellingly associated with TS attributes.

• #28 Epigenetics in Turner syndrome | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0477-0

  However, epigenetic effects have been poorly investigated in TS as, up to now, most of the TS research has focused on clinical, chromosomal, and genetic abnormalities. […] While haploinsufficiency of genes on the X chromosome has been the focus of recent research, underlying epigenetic mechanisms have been poorly studied in TS. […] Nevertheless, it is has become clear that epigenetic processes are altered in TS, so that by modulating gene expression, epigenetics could play a crucial role in altered growth and in the development of abnormalities of lipid and glucose metabolism associated with TS. […] An interesting finding of all these studies is that methylation-based and expression-based pathway analyses are complementary, rather than overlapping, and are correlated with the clinical picture displayed by TS subjects.

• #29 Epigenetics in Turner syndrome | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0477-0

  Thus, a genome-wide hypomethylation has been described in leukocytes from 45,X patients, which might reactivate cryptic site transcription start and cause changes in expression of isoform transcripts. […] The clinical consequences logic attributed to 45,X are direct dosage effects of genes on the sexual chromosomes, i.e., TS is due to complete or partial loss of DNA sequences in the second sex chromosome which provokes haploinsufficiency of genes that are normally biallelically expressed from both sex chromosomes and escape from X chromosome inactivation. […] The absence of the second sexual chromosome in TS has led authors to speculate that there may be genes present on the X chromosome which are expressed differently depending upon whether they are maternally or paternally inherited.

• #30 Turner syndrome: narrative review of genetics and clinical aspects of management – Fudge – Pediatric Medicine

  https://pm.amegroups.org/article/view/7267/html

  Tissue inhibitor matrix metalloproteinase 1 (TIMP1) and TIMP3 have been linked to increased risk of bicuspid aortic valve and aortic dilation, although additional validation studies are needed. […] Epigenetic mechanisms such as differential methylation and copy number variations may be involved in the development of the TS phenotype. […] Genome-wide copy number variations were found to be increased in TS in one study which postulated this mechanism as a potential contributor to the development of congenital heart disease in TS. […] Women with TS compared to 46,XX women have a hypomethylated genome with fewer areas of hypermethylation, and differences in RNA expression involving X chromosome and autosomal genes. […] Knowledge about the complex genetic factors involved in the development of the TS phenotype is advancing, which could improve our understanding of this condition, and potentially lead to new therapeutic strategies.

• #31 Turner Syndrome

  https://www.mdpi.com/2673-396X/3/2/22

  This gene’s function is dosage-dependent, with decreased gene expression or haploinsufficiency leading to short stature and other features such as Madelung deformity, high arched palate, scoliosis and micrognathia. […] Epigenetic differences that influence gene expression without altering base sequences exist between 45,X and 46,XX individuals, with extensive hypomethylation throughout 45,X genome compared to 46,XX individuals, apart from differences in hypermethylation. […] Epigenetic modification and resulting altered gene expression can contribute to various pathogenesis seen in TS. […] Underlying pathogenesis mechanism in various TS phenotypic presentation is evolving with improved understanding of notable difference in RNA expression, autosomal DNA methylation and X chromosome methylation in TS patients.

• #32 Epigenetics in Turner syndrome | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0477-0

  However, no human genomic imprinted genes on the X chromosomes have been identified, and no significant skewed parental origin effect of the clinical features of TS patients has been recognized, with the exception of those exhibiting sexual dimorphism. […] Therefore, from a clinical perspective, a genetic work-up to detect the parental origin of the remaining X is currently not indicated in routine care of women with TS. […] The TS phenotype may therefore likely arise from an abnormal connection of various genetic and epigenetic factors whose primary source is the monosomy of the second sex chromosome. […] Increasing evidence suggests that TS features could be caused by altered regulation and complex interrelations of many genes both on and outside both sex chromosomes.

• #33 Clinical and genetic aspects of Turner’s syndrome | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-clinical-genetic-aspects-turner39s-syndrome-S1665579616300503

  Turner’s syndrome, or monosomy X, is defined as the total or partial loss of the second sex chromosome. The clinical phenotype is highly variable and includes short stature, gonadal dysgenesis, pterygium colli, cubitus valgus and low hairline. […] Understanding its complex etiology and learning more about its clinical variability and complications will allow us to advance the therapeutic and management approach of such patients. […] The variable expressivity of height and other physical features may be only partially related to the chromosomal formula, even when most recent studies do not show a clear genotype-phenotype correlation. […] The Turner’s syndrome phenotype can be explained by a haploinsufficiency of the genes which are normally expressed in both sexual chromosomes and which escape X inactivation.

• #34 Turner Syndrome where are we? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03337-0

  Turner syndrome (TS) results from the loss of one X chromosome in phenotypic females, leading to a range of complications such as short stature, cardiovascular issues, autoimmune disorders, metabolic imbalances, osteoporosis, neurocognitive deficits, hearing loss, abnormalities in endocrine functions, infertility, disruptions in bone metabolism, and neurocognitive deficits. […] Turner Syndromes phenotype and genotype correlations are generally poor, and the exact cause remains incompletely understood. However, it is believed to result from both genomic imbalances induced by sex chromosome genes and the additive effect of epigenetic factors on linked genes within gene networks. […] The short stature homeobox-containing gene (SHOX) regulates growth, and its haploinsufficiency contributes to the characteristic short stature in TS.

• #35 Orphanet: Turner syndrome

  https://www.orpha.net/en/disease/detail/881

  A rare chromosomal anomaly syndrome characterized by complete or partial loss of an X chromosome in phenotypic females, clinically manifesting with short stature, primary ovarian insufficiency as well as cardiovascular, renal, liver, autoimmune diseases, hearing loss and neurocognitive abnormalities. […] X monosomy is the most common underlying etiology, while some cases have mosaicism or structural X chromosome anomalies. Clinical signs are more severe in patients with 45,X monosomy than in 45,X/46,XX or 45,X/46,XX/47,XXX mosaicism. Patients with an X isochromosome have a higher risk of liver and autoimmune diseases, while those with a ring chromosome are more prone to growth retardation and metabolic disorders. Haploinsufficiency of the SHOX gene is a well-established cause of short stature. The presence of Y material is related to the occurrence of gonadoblastoma.

• #36 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  Increased susceptibility to gonadoblastomas are seen in those individuals with Y chromosomal abnormality karyotypes. […] Presence of autoimmune diseases may be due to haploinsufficiency of X chromosome or due to proinflammatory cytokines such as IL-6, IL-8 and tumor necrosis factor alpha. […] While phenotype-karyotype correlations are unreliable in predicting clinical features in Turner syndrome, some studies have suggested the following: Loss of short and long arm of X chromosome decreased ovarian function, number and survival of oocytes. […] Loss of interstitial or terminal long arm of X chromosome Short stature, primary or secondary ovarian failure. […] Loss of a region at Xp22.3 Neurocognitive problems. […] Loss of a region at Xp11.4 Critical for the development of lymphedema. […] Presence of an isochromosome Xq Increased risk of hypothyroidism and inflammatory bowel disease. […] Presence of ring chromosome Increased risk of mental retardation. […] Lack of the XIST locus Phenotype with more severe mental retardation.

• #37 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  Short stature, which is one of the most frequently observed clinical features, can be explained by SHOX haplo-insufficiency. Therefore, while short stature is more frequently present in patients with 46,X,i(Xq) karyotype, gonadal dysfunction is more likely to be seen in patients with 46,X,i(Xp) karyotype, which is a very rare entity. […] The incidence of autoimmune thyroid disease in TS increases with advanced age. Recently, a twofold increase in the prevalence of autoimmune thyroid disease has been observed from the first to the third decade of life in patients with the isochromosome karyotype. In addition, patients with 45,X or 46,X,i(Xq) karyotype carry a higher risk of developing hearing loss when compared to patients with mosaic karyotypes. A linear relationship was also found between age and hearing loss.

• #38 Organ Abnormalities Caused by Turner Syndrome

  https://www.mdpi.com/2073-4409/12/10/1365

  Turner syndrome (TS), a genetic disorder due to incomplete dosage compensation of X-linked genes, affects multiple organ systems, leading to hypogonadotropic hypogonadism, short stature, cardiovascular and vascular abnormalities, liver disease, renal abnormalities, brain abnormalities, and skeletal problems. […] The SHOX gene plays a crucial role in short stature and abnormal skeletal phenotype in patients with TS. […] Total or partial loss of one of the two sex chromosomes affects biological pathways and networks, and, in some cases, SHOX gene defects have been linked to certain phenotypes of TS. […] Accelerated germ cell death is presumed to be the major mechanism causing germ cell depletion in patients with TS. […] TS also affects brain structure and function. […] The primary cause of TS is the haploinsufficiency of genes located on the X chromosome. Complete or partial loss of one of the two X chromosomes contributes to the insufficiency of X-linked genes.

• #39 Turner Syndrome – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/chromosome-and-gene-abnormalities/turner-syndrome

  Gonadal dysgenesis (ovaries replaced by bilateral streaks of fibrous stroma and devoid of developing ova) occurs in 90% of females. […] The characteristic findings are ovaries with some connective tissue with either no or few follicles (termed streak gonads). […] It is important to note that people with 1 X chromosome who have mosaicism involving a Y chromosome (ie, some cells with 46,XY) may have a male or female phenotype. […] Deletion of the X chromosomes short arm seems to play an important role in producing the typical phenotype. […] Gonadal dysgenesis results in premature ovarian failure in most patients, manifested by absent or incomplete pubertal development, lack of breast development, amenorrhea (most patients have primary amenorrhea, but some have menarche and then secondary amenorrhea due to gonadal dysgenesis with premature ovarian failure), and infertility. […] Other medical problems that are associated with Turner syndrome develop with aging and may not be evident without screening.

• #40 Turner Syndrome – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/chromosome-and-gene-abnormalities/turner-syndrome

  Gonadal dysgenesis (ovaries replaced by bilateral streaks of fibrous stroma and devoid of developing ova) occurs in 90% of females. […] The characteristic findings are ovaries with some connective tissue with either no or few follicles (termed streak gonads). […] It is important to note that people with 1 X chromosome who have mosaicism involving a Y chromosome (ie, some cells with 46,XY) may have a male or female phenotype. […] Deletion of the X chromosomes short arm seems to play an important role in producing the typical phenotype. […] Gonadal dysgenesis results in premature ovarian failure in most patients, manifested by absent or incomplete pubertal development, lack of breast development, amenorrhea (most patients have primary amenorrhea, but some have menarche and then secondary amenorrhea due to gonadal dysgenesis with premature ovarian failure), and infertility. […] Other medical problems that are associated with Turner syndrome develop with aging and may not be evident without screening.

• #41 Turner Syndrome | Oncohema Key

  https://oncohemakey.com/turner-syndrome-2/

  The short stature homeobox containing gene on the X chromosome (SHOX) is the most cited example. […] The concept of haploinsufficiency of a gene, such as SHOX located in the PAR, is an attractive explanation for part of the TS phenotype. […] However, there is currently little evidence of any other monogenic variants on the PARs associated with the TS phenotype. […] Initial reports on the presence of gonadal pathology described TS individuals as having streak ovaries. […] This suggests a process of accelerated oocyte demise and follicular atresia. […] The chromosomal location of putative genes important for fertility has yet to be defined. […] The strongest predictor for the presence of ovarian follicles is a karyotype with mosaicism for 45,X and 46,XX cell lines. […] The risk of gonadoblastoma based on the best evidence available is roughly 10% if Y chromosome material is present. […] The major cardiovascular complications include aortic valve disease and aortic dilation, dissection, or even rupture.

• #42 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  A study of 67 Turner syndrome in China found 50 percent of the patients with the classic 45 X karyotype followed by the mosaic pattern, a chromosomal structural abnormality (isochromosome or ring chromosome) and a Y chromosomal structural abnormality. […] Turner syndrome might be due to the partial or complete absence of these inactivated genes and the presence of functional homologues of the Y chromosome. […] Short Stature is said to be due to the haploinsufficiency of the short stature homeobox (SHOX gene) which is located on the pseudoautosomal region of the X chromosome. […] The SHOX gene is also responsible for skeletal abnormalities such as high arched palate, abnormal auricular development, cubitus valgus, genu valgum, Madelung deformity and short metacarpals. […] Premature ovarian failure is secondary to ovarian dysgenesis and early follicular apoptosis.

• #43 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  The cytogenetic studies have shown that the region between Xq13 and Xq28 is important for normal ovarian function. The Xq13-q21 region is defined as the critical region (CR) 1, and the proximal deletions of this region are usually compatible with normal menstruation and fertility. The terminal and interstitial deletions of the CR2 at Xq23-q28 are mostly responsible for premature ovarian failure. The FMR1 gene, which is important in the ovarian function, is localized in the Xq27.3 locus, and expansions in the exon 1 triplet repeat of the gene are associated with an increased risk of early menopause. […] Approximately 50% of TS patients have 45,X karyotype and the most common structural X chromosome abnormality is isochromosome Xq. The retained X chromosome is maternally derived in two thirds of the patients. The patients with 46,XY cell line mosaicism or structural rearrangement of the Y chromosome mostly have masculinized external genitalia and are at increased risk of developing gonadoblastoma and other gonadal tumors, whereas patients with mosaic 46,XX karyotype or isochromosome Xq have a milder phenotype.

• #44 What is Turner Syndrome? And Why Does It Affect Only Females?

  https://www.webmd.com/children/what-is-turner-syndrome

  Turner syndrome happens when a female is missing certain genes normally on the X chromosome. […] Some people with Turner syndrome are missing a whole copy of the X chromosome. For others, just a part of the X chromosome containing a specific set of genes is missing. Almost 99% of babies with a missing X chromosome are miscarried, but about 1% of them are born with Turner syndrome. […] Turner syndrome may increase your risk of bone diseases such as osteoporosis, scoliosis, and bone fractures. […] With Turner syndrome, you may have potentially life-threatening heart and blood vessel problems. At least 50% of people with Turner Syndrome have a heart condition present at birth. […] Turner syndrome can be linked to other health conditions, such as heart problems because of its physical structure. […] Turner syndrome can’t be cured because it involves a problem with your genetic makeup.

• #45 Turner Syndrome where are we? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03337-0

  The increased prevalence of bicuspid aortic valve in TS is also linked with karyotype and is most common in women with the 45, X karyotype. […] The imbalance of TIMP1 and TIMP3 contributes to the increased vulnerability to aortic morphological abnormalities. […] TS is primarily not inherited, with most cases involving monosomy involving the mothers X chromosome. […] The actual etiology of the higher occurrence of autoimmune thyroid diseases in females with TS remains unknown; however, a number of hypotheses have been put forward to understand the phenomenon. […] The high risk of autoimmunity in TS females has been recognized as one of the more prominent characteristics of the condition. […] The specific processes behind this increased vulnerability to autoimmunity remain poorly understood.

• #46 Turner Syndrome where are we? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03337-0

  The increased prevalence of bicuspid aortic valve in TS is also linked with karyotype and is most common in women with the 45, X karyotype. […] The imbalance of TIMP1 and TIMP3 contributes to the increased vulnerability to aortic morphological abnormalities. […] TS is primarily not inherited, with most cases involving monosomy involving the mothers X chromosome. […] The actual etiology of the higher occurrence of autoimmune thyroid diseases in females with TS remains unknown; however, a number of hypotheses have been put forward to understand the phenomenon. […] The high risk of autoimmunity in TS females has been recognized as one of the more prominent characteristics of the condition. […] The specific processes behind this increased vulnerability to autoimmunity remain poorly understood.

• #47 Turner syndrome: narrative review of genetics and clinical aspects of management – Fudge – Pediatric Medicine

  https://pm.amegroups.org/article/view/7267/html

  Tissue inhibitor matrix metalloproteinase 1 (TIMP1) and TIMP3 have been linked to increased risk of bicuspid aortic valve and aortic dilation, although additional validation studies are needed. […] Epigenetic mechanisms such as differential methylation and copy number variations may be involved in the development of the TS phenotype. […] Genome-wide copy number variations were found to be increased in TS in one study which postulated this mechanism as a potential contributor to the development of congenital heart disease in TS. […] Women with TS compared to 46,XX women have a hypomethylated genome with fewer areas of hypermethylation, and differences in RNA expression involving X chromosome and autosomal genes. […] Knowledge about the complex genetic factors involved in the development of the TS phenotype is advancing, which could improve our understanding of this condition, and potentially lead to new therapeutic strategies.

• #48 Turner Syndrome Pathogenesis and Clinical Findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/turner-syndrome-pathogenesis-and-clinical-findings/turner-syndrome-pathogenesis-and-clinical-findings/

  Turner Syndrome: Pathogenesis and clinical findings […] Non-disjunction in phenotypically female gametes (i.e. homologous X-chromosomes or sister chromatids fail to separate) […] Partial or complete absence of second sex chromosome, leaving only one normal X-chromosome […] Possible Chromosomal Profiles Other meiotic error deletion or misdivision of X-chromosomal material […] Complete loss of one X-chromosome in all cells (45,X) (45%) […] Expression of SHOX gene (present on X- and Y-chromosomes) […] Cellular proliferation in growth plates of bones in extremities during embryonic development […] Congenital Heart Defects (most serious) […] Single copy of TIMP1 gene and presence of risk TIMP3 allele, and differential expression of KDM6A gene […] One X-chromosome and presence of Y-chromosomal material in some or all cells (e.g., 45,X/46,XY)

• #49 Clinical and genetic aspects of Turner’s syndrome | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-clinical-genetic-aspects-turner39s-syndrome-S1665579616300503

  The SHOX gene (short-stature homebox) located in Xp22.23 (PAR1) belongs to the homebox gene family, which is a transcriptional regulator and key controller of multiple processes during embryonic development. […] Other genes located in the short arm of the X chromosome may contribute to the variability observed in the delay in growth. […] Although there are no genetic findings which explain visceral and soft tissue affectation, some phenotypical data such as lymphedema, pterigium colli and cardiac abnormalities have been linked with lymphatic hypoplasia attributable to other genes which escape X chromosome inactivation and are located in the Xp11.39 region. […] Since structural alterations of the heart and vascular system are much more common in girls with cystic hygroma or lymphedema, it has been suggested that abnormal lymph nodes are involved in the development of these heart diseases.

• #50 Clinical and genetic aspects of Turner’s syndrome | Medicina Universitaria

  https://www.elsevier.es/en-revista-medicina-universitaria-304-articulo-clinical-genetic-aspects-turner39s-syndrome-S1665579616300503

  The X chromosome contains 155 million pairs of bases (pb) and over 1000 genes while the Y chromosome has a length of 60 million pb and contains over 200 genes, from which only 48 are codifiers. […] The PAR1 region covers 2.6Mb of the short arm of X and Y human chromosomes. […] The PAR2 region is in the distal end of the long arm, and is much smaller since it only covers 320kb. […] Women with TS have a greater prevalence of autoimmune diseases such as Hashimoto thyroiditis, celiac disease and ulcerative colitis.

• #51 Turner syndrome: mechanisms and management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/31213699/

  Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. […] Turner syndrome is associated with short stature, delayed puberty, ovarian dysgenesis, hypergonadotropic hypogonadism, infertility, congenital malformations of the heart, endocrine disorders such as type 1 and type 2 diabetes mellitus, osteoporosis and autoimmune disorders. […] Here, we present an updated Review of Turner syndrome, covering advances in genetic and genomic mechanisms of disease, associated disorders and multidisciplinary approaches to patient management, including growth hormone therapy and hormone replacement therapy.

• #52 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  Increased susceptibility to gonadoblastomas are seen in those individuals with Y chromosomal abnormality karyotypes. […] Presence of autoimmune diseases may be due to haploinsufficiency of X chromosome or due to proinflammatory cytokines such as IL-6, IL-8 and tumor necrosis factor alpha. […] While phenotype-karyotype correlations are unreliable in predicting clinical features in Turner syndrome, some studies have suggested the following: Loss of short and long arm of X chromosome decreased ovarian function, number and survival of oocytes. […] Loss of interstitial or terminal long arm of X chromosome Short stature, primary or secondary ovarian failure. […] Loss of a region at Xp22.3 Neurocognitive problems. […] Loss of a region at Xp11.4 Critical for the development of lymphedema. […] Presence of an isochromosome Xq Increased risk of hypothyroidism and inflammatory bowel disease. […] Presence of ring chromosome Increased risk of mental retardation. […] Lack of the XIST locus Phenotype with more severe mental retardation.

• #53 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  Short stature, which is one of the most frequently observed clinical features, can be explained by SHOX haplo-insufficiency. Therefore, while short stature is more frequently present in patients with 46,X,i(Xq) karyotype, gonadal dysfunction is more likely to be seen in patients with 46,X,i(Xp) karyotype, which is a very rare entity. […] The incidence of autoimmune thyroid disease in TS increases with advanced age. Recently, a twofold increase in the prevalence of autoimmune thyroid disease has been observed from the first to the third decade of life in patients with the isochromosome karyotype. In addition, patients with 45,X or 46,X,i(Xq) karyotype carry a higher risk of developing hearing loss when compared to patients with mosaic karyotypes. A linear relationship was also found between age and hearing loss.

• #54 What Is Turner Syndrome? – Turner Syndrome Foundation Email EmailEvent Series

  https://turnersyndromefoundation.org/what_is_turner_syndrome/?srsltid=AfmBOorDexFKpfoW–hmYeXGWvcSPVuEjQpSXqm_6B86RUjexUPhQzv8

  The gene on the X chromosome that is responsible for most of the features of Turner syndrome is still undetermined. Ultimately, the specific cause of Turner is unknown. However, researchers have been able to identify the gene responsible for short stature and skeletal abnormalities, which is the SHOX gene. The SHOX gene is important for bone development and growth. […] Turner Syndrome is a spectrum disorder, consisting of major symptoms and signs, all of which may or may not be present. Health concerns include but are not limited to cardiovascular disease, issues with the kidneys and thyroid, diabetes and hearing deficiencies. Early intervention has been proven to produce long-term positive outcomes. […] Approximately 30% of individuals with Turner syndrome are reported to have “bicuspid aortic valves,” meaning that the major blood vessel from the heart has only two rather than three components to the valve regulating blood flow, missed diagnosis of this cardio-vascular disease could have grave outcomes. The cognitive function and educational issues affecting some girls and women with Turner syndrome may include difficulty with visual spatial tasks, memory, and attention, as well as other learning disabilities. Other consequences of this disorder include risk of ovarian failure, Type II diabetes, hyporthyroidism. The psychosocial issues associated with Turner syndrome include low-self-esteem, predisposition to age-specific problems isolation, depression and with psychosocial adaptation.

• #55 Turner syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Turner_syndrome_pathophysiology

  Increased susceptibility to gonadoblastomas are seen in those individuals with Y chromosomal abnormality karyotypes. […] Presence of autoimmune diseases may be due to haploinsufficiency of X chromosome or due to proinflammatory cytokines such as IL-6, IL-8 and tumor necrosis factor alpha. […] While phenotype-karyotype correlations are unreliable in predicting clinical features in Turner syndrome, some studies have suggested the following: Loss of short and long arm of X chromosome decreased ovarian function, number and survival of oocytes. […] Loss of interstitial or terminal long arm of X chromosome Short stature, primary or secondary ovarian failure. […] Loss of a region at Xp22.3 Neurocognitive problems. […] Loss of a region at Xp11.4 Critical for the development of lymphedema. […] Presence of an isochromosome Xq Increased risk of hypothyroidism and inflammatory bowel disease. […] Presence of ring chromosome Increased risk of mental retardation. […] Lack of the XIST locus Phenotype with more severe mental retardation.

• #56 Turner Syndrome Pathogenesis and Clinical Findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/turner-syndrome-pathogenesis-and-clinical-findings/turner-syndrome-pathogenesis-and-clinical-findings/

  Turner Syndrome: Pathogenesis and clinical findings […] Non-disjunction in phenotypically female gametes (i.e. homologous X-chromosomes or sister chromatids fail to separate) […] Partial or complete absence of second sex chromosome, leaving only one normal X-chromosome […] Possible Chromosomal Profiles Other meiotic error deletion or misdivision of X-chromosomal material […] Complete loss of one X-chromosome in all cells (45,X) (45%) […] Expression of SHOX gene (present on X- and Y-chromosomes) […] Cellular proliferation in growth plates of bones in extremities during embryonic development […] Congenital Heart Defects (most serious) […] Single copy of TIMP1 gene and presence of risk TIMP3 allele, and differential expression of KDM6A gene […] One X-chromosome and presence of Y-chromosomal material in some or all cells (e.g., 45,X/46,XY)

• #57 Turner syndrome | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/Turner-syndrome

  Turner syndrome, relatively uncommon sex-chromosome disorder that causes aberrant sexual development in human females. […] Turner syndrome occurs when one sex chromosome is deleted, so that instead of the normal 46 chromosomes, of which two are sex chromosomes (XX in females and XY in males), the chromosomal complement is 45,X. […] In genetic terms, these patients are neither male nor female because the second, sex-determining chromosome is absent. […] However, phenotypically, affected individuals develop as females because there is no Y chromosome to direct the fetal gonads to the male configuration. […] In genetic terms, Turner syndrome is common: one-tenth of all spontaneously aborted fetuses have a 45,X chromosome constitution, and only 3 percent of affected fetuses survive to term.

• #58 Laboratory guideline for Turner syndrome | Genetics in Medicine

  https://www.nature.com/articles/gim20108

  Turner syndrome is a disorder that has distinct clinical features and has karyotypic aberrations with loss of critical regions of the X chromosome. […] A majority of genes associated with the physical features observed in Turner syndrome are located on Xp (Xp11.2-p22); loci contributing to ovarian function reside in Xq (Xq24). […] The disease incidence is approximately 1 in 2500 liveborn females. A 45,X karyotype is observed in 1% to 2% of conceptuses, 10% of miscarriages and 1% of stillbirths. Greater than 99% of 45,X conceptuses result in spontaneous loss, usually before 28 weeks. […] Apparently nonmosaic monosomy X is found in 45% of patients with Turner syndrome postnatally. A structural chromosome abnormality or mosaicism for 45,X and another cell line is found in the lymphocytes of the remaining patients with Turner syndrome.

• #59 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  The pseudoautosomal regions (PAR) of X and Y chromosomes are both necessary for normal development. It has been reported that haplo-insufficiency in the CSF2RA gene located in the PAR1 region, which plays a role in normal placental development, is responsible for high mortality in 45,X karyotype embryos. Recently, it has been suggested that all living patients in whom TS with 45,X karyotype has been diagnosed, are cryptic mosaics. Loss of X chromosome in these embryos frequently result in mitotic error, but it has been reported that this loss may occur at various stages of postfertilization.

• #60 Turner’s Syndrome – WikiLectures

  https://www.wikilectures.eu/w/Turner%27s_Syndrome

  From the cytogenetic point of view there is a certain link between Turner syndrome cases, it is the absence of the entire X chromosome or the deletion of some of its parts. Pathological is therefore the absence of certain genes which would otherwise be present. However, it is necessary to approach this problem more closely, because males (46,XY karyotype) also have only a single X chromosome and even in women with the complete karyotype (46,XX) is one of the two X chromosomes inactivated. […] It is nonetheless important that some genes on the inactivated X chromosome continue being transcribed regardless (therefore they are exceptionally interesting in regards to the pathogenesis of Turner syndrome). These genes can be classified into three groups: […] Since the X chromosome doesn’t have to be missing entirely only some genes the phenotype of the affected individuals can be different depending on which genes are missing. The most severe is exactly the simple 45,X monosomy (it is recorded that up to 99% of the fetuses with this karyotype are miscarried), forms with only specific structural aberrations of the second X chromosome or mosaic forms are clinically less severe (an opinion exists which states that simple 45,X monosomy is incompatible with survival and the living bearers of this karyotype are actually unrecognized mosaics).

• #61 Turner Syndrome and Its Variants – The Journal of Pediatric Research

  https://jpedres.org/articles/turner-syndrome-and-its-variants/doi/jpr.35744

  The pseudoautosomal regions (PAR) of X and Y chromosomes are both necessary for normal development. It has been reported that haplo-insufficiency in the CSF2RA gene located in the PAR1 region, which plays a role in normal placental development, is responsible for high mortality in 45,X karyotype embryos. Recently, it has been suggested that all living patients in whom TS with 45,X karyotype has been diagnosed, are cryptic mosaics. Loss of X chromosome in these embryos frequently result in mitotic error, but it has been reported that this loss may occur at various stages of postfertilization.

• #62 Epigenetics in Turner syndrome | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0477-0

  However, no human genomic imprinted genes on the X chromosomes have been identified, and no significant skewed parental origin effect of the clinical features of TS patients has been recognized, with the exception of those exhibiting sexual dimorphism. […] Therefore, from a clinical perspective, a genetic work-up to detect the parental origin of the remaining X is currently not indicated in routine care of women with TS. […] The TS phenotype may therefore likely arise from an abnormal connection of various genetic and epigenetic factors whose primary source is the monosomy of the second sex chromosome. […] Increasing evidence suggests that TS features could be caused by altered regulation and complex interrelations of many genes both on and outside both sex chromosomes.

• #63 Turner Syndrome where are we? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03337-0

  TS management requires a holistic approach that includes hormonal, cardiovascular, psychosocial, and reproductive aspects. […] This holistic understanding of TS pathogenesis will pave the way for targeted therapeutic interventions and this type of integration holds promise for personalized medicine-enhanced therapeutic strategies and a deeper understanding of the syndromes genetic basis and lessens the burden of TS patients.

• #64 Turner Syndrome where are we? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03337-0

  TS management requires a holistic approach that includes hormonal, cardiovascular, psychosocial, and reproductive aspects. […] This holistic understanding of TS pathogenesis will pave the way for targeted therapeutic interventions and this type of integration holds promise for personalized medicine-enhanced therapeutic strategies and a deeper understanding of the syndromes genetic basis and lessens the burden of TS patients.

• #65 Human 45,X Fibroblast Transcriptome Reveals Distinct Differentially Expressed Genes Including Long Noncoding RNAs Potentially Associated with the Pathophysiology of Turner Syndrome | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100076

  Our observations manifest that X monosomy affects the transcriptomic profile of the cells and differential regulation of genes in Turner syndrome could be the key features to establish genotype-phenotype relation. Many of the characteristic phenotypes observed in the X monosomy condition could also be putatively correlated to the functions of differentially expressed gene sets. In this study, altered gene expression related to the haploinsufficiency and dosage effect suggests the involvement of critical molecular genetic pathways governing bone formation, glucose metabolism, and gonadal functioning.

• #66 Turner syndrome: narrative review of genetics and clinical aspects of management – Fudge – Pediatric Medicine

  https://pm.amegroups.org/article/view/7267/html

  Tissue inhibitor matrix metalloproteinase 1 (TIMP1) and TIMP3 have been linked to increased risk of bicuspid aortic valve and aortic dilation, although additional validation studies are needed. […] Epigenetic mechanisms such as differential methylation and copy number variations may be involved in the development of the TS phenotype. […] Genome-wide copy number variations were found to be increased in TS in one study which postulated this mechanism as a potential contributor to the development of congenital heart disease in TS. […] Women with TS compared to 46,XX women have a hypomethylated genome with fewer areas of hypermethylation, and differences in RNA expression involving X chromosome and autosomal genes. […] Knowledge about the complex genetic factors involved in the development of the TS phenotype is advancing, which could improve our understanding of this condition, and potentially lead to new therapeutic strategies.

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