Materiały źródłowe

• #1 Albinism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519018/

  Albinism is a group of heritable conditions associated with decreased or absent melanin in ectoderm-derived tissues (most notably the skin, hair, and eyes), yielding a characteristic decrease in skin pigmentation. […] Albinism, in any of its forms, is the result of heritable mutations that lead to defective melanocytes, unable to properly synthesize melanin or distribute it through dermal tissues. […] Melanocytes are derived from neural crest ectoderm during embryonic development and migrate into the skin, eyes, hair, and inner ear. […] The first (and rate-limiting) step in eumelanin synthesis involves the oxidation of L-tyrosine to DOPA by tyrosinase. […] Mutations in the tyrosinase gene, as seen in OCA1A, leads to complete loss of the ability to produce eumelanin. […] The two significant results of hypomelanosis can be divided into dermatological and ophthalmologic consequences.

• #1 Albinism: for professionals – Gene Vision

  https://gene.vision/knowledge-base/albinism-for-doctors/

  Pathogenic mutations in 18 genes have been identified to cause OCA (syndromic/non-syndromic) or OA by affecting melanin biosynthesis or melanin distribution in dermal tissues. […] Melanin is synthesised from an organelle called melanosomes which are located inside melanocytes. Melanocytes are derived from the neural crest ectoderm during embryonic development and migrate into the skin, hair, eyes and inner ear to fulfil their primary function. Melanogenesis is tightly regulated by the activity of tyrosinase. It converts L-tyrosine to L-DOPA or dopaquinone for the production of eumelanin (brown to black colour) or pheomelanin (red to yellow colour), two common forms of melanin in humans. […] Apart from its role in protecting the skin from harmful ultraviolet (UV) rays, melanin is also crucial to the development of ocular structures and neural pathways. It induces the formation of fovea, optic nerves, optic tracts and visual cortex, along with triggering the crossover of optic nerve fibres from each eye at the chiasm to the contralateral occipital lobe, which is essential for binocular vision.

• #1 Albinism: Types, Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/21747-albinism

  Albinism is a rare genetic condition caused by mutations, or changes, of certain genes that affect the amount of melanin your body produces. […] Variations in the genes responsible for melanin production cause albinism. Specific genes associated with oculocutaneous albinism include: TYR, OCA2, TYRP1, SLC45A2. […] Variations in the GPR143 gene are associated with ocular albinism. […] Oculocutaneous albinism (OCA) follows an autosomal recessive pattern of inheritance. This means you must inherit an albinism gene from both of your biological parents to develop the condition yourself. […] Ocular albinism (OA) usually follows an X-linked pattern of inheritance. This means the genetic variation is passed through the X chromosome. OA mostly occurs in males.

• #1 Albinism

  https://www.nhs.uk/conditions/albinism/

  Albinism affects the production of melanin, the pigment that colours skin, hair and eyes. […] The reduced amount of melanin can cause eye problems. This is because melanin is involved in the development of the retina, the thin layer of cells at the back of the eye. […] In all types of OCA and some types of OA, albinism is passed on in an autosomal recessive inheritance pattern. This means a child has to get 2 copies of the gene that causes albinism (1 from each parent) to have the condition. […] Most types of OA are passed on in an X-linked inheritance pattern. This pattern affects boys and girls differently: girls who get the albinism gene usually become carriers only, while boys who get it will have albinism.

• #1 Germline and somatic albinism variants in amelanotic/hypomelanotic melanoma: Increased carriage of TYR and OCA2 variants | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238529

  Albinism is a group of severe genetic disorders characterized by reduced or absent biosynthesis of melanin pigment in melanocytes of the skin, hair follicles and eyes. It has been classically subdivided into three groups: oculocutaneous (OCA), ocular (OA), and syndromic albinism. Most forms of OCA are characterized by features including nystagmus, foveal hypoplasia, iris transillumination, and photophobia. All seven known types of non-syndromic OCA are autosomal recessive in inheritance. OCA1A is characterized by the complete absence of melanin production throughout life due to the absence of TYR gene activity. The OCA1B subtype is a milder form that displays some pigment accumulation over time with a low degree of retained tyrosinase (TYR) enzyme activity. Other albinism classes are: OCA2 caused by deletion or loss of activity of the melanosomal P-protein (OCA2 gene); OCA3 attributable to mutations in TYRP1; OCA4 due to loss of SLC45A2; and OCA5 which is linked to chromosome 4q24, with the responsible gene yet to be characterized. More recently OCA6 and OCA7 have been identified with mutations in SLC24A5 and the LRMDA genes respectively. Of those who receive a molecular diagnosis, OCA1 and OCA2 account for 42% and 28% of cases respectively.

• #1 Albinism: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1200472-overview

  The term albinism originates from the word, albus (Latin for white), and it is an inherited disorder characterized by reduced pigmentation. Albinism is caused by pathogenic variants in genes important for melanin synthesis. […] The melanin pathway consists of a series of reactions that converts tyrosine into 2 types of melanin: 1) black-brown eumelanin and 2) red-blond pheomelanin. Genetic variants affecting proteins/enzymes along this pathway inevitably result in reduced melanin production. […] The development of the ocular system is highly dependent on the presence of melanin. Absent or decreased melanin can cause abnormal crisscrossing of optic nerve fibers as a result of misdirected retinogeniculate projections. Melanin is believed to control neuronal target specificity in the brain. In cases of incomplete pigmentation, the developing optic tracts almost entirely intersect at the chiasm, whereas in individuals without albinism, almost half (45%) of axons beginning in the temporal half of the retina pass through the chiasm uncrossed and project to the same-sided lateral geniculate nucleus. […] This results in predominantly monocular vision and reduced binocular depth perception.

• #1 Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism – PubMed

  https://pubmed.ncbi.nlm.nih.gov/10094567/

  Albinism, caused by a deficiency of melanin pigment in the skin, hair, and eye (oculocutaneous albinism [OCA]), or primarily in the eye (ocular albinism [OA]), results from mutations in genes involved in the biosynthesis of melanin pigment. […] The lack of melanin pigment in the developing eye leads to fovea hypoplasia and abnormal routing of the optic nerves. […] Mutations in six genes have been reported to be responsible for different types of oculocutaneous and ocular albinism, including the tyrosinase gene (TYR) and OCA1 (MIM# 203100), the OCA2 gene and OCA2 (MIM# 203200), the tyrosinase-related protein-1 gene (TYRP1) and OCA3 (MIM# 203290), the HPS gene and Hermansky-Pudlak syndrome (MIM# 203300), the CHS gene (CHS1), and Chediak-Higashi syndrome (MIM# 214500), and the X-linked ocular albinism gene and OA1 (MIM#300500).

• #1

  https://omim.org/entry/203100

  A number sign (#) is used with this entry because oculocutaneous albinism type IA (OCA1A) is caused by homozygous or compound heterozygous mutation in the tyrosinase gene (TYR; 606933) on chromosome 11q14. […] Oculocutaneous albinism is a genetically heterogeneous congenital disorder characterized by decreased or absent pigmentation in the hair, skin, and eyes. The term 'albinism’ includes specific ocular changes that are the results of reduced amounts of melanin in the developing eye; these abnormalities in the eye and optic system are specific and necessary for the diagnosis. […] OCA1, caused by mutations in the TYR gene, is divided clinically into 2 types: type IA, OCA1A, characterized by complete lack of tyrosinase activity due to production of an inactive enzyme, and type IB (OCA1B; 606952), characterized by reduced activity of tyrosinase.

• #1 Orphanet: Oculocutaneous albinism type 2

  https://www.orpha.net/en/disease/detail/79432

  A form of oculocutaneous albinism characterized by variable hypopigmentation of the skin and hair, numerous characteristic ocular changes and misrouting of the optic nerves at the chiasm. […] OCA2 is caused by a mutation in the OCA2 gene (15q12-q13), encoding the OCA2 protein. The precise function of this protein is unknown, however, several studies have reported possible roles in the maintenance of proper intramelanosomal pH or the melanosomal structural matrix. […] Patients with OCA2 have melanocytes that still produce small amounts of melanin, but it is mostly yellow pheomelanin.

• #1 Albinism and Other Genetic Disorders of Pigmentation | Plastic Surgery Key

  https://plasticsurgerykey.com/albinism-and-other-genetic-disorders-of-pigmentation/

  The pathogenesis of OCA3 remains poorly understood because the normal function of Tyrp1 in human melanocytes is still being clarified. […] TYRP1 and tyrosinase reciprocally stabilize each other through associations in the endoplasmic reticulum, with mutations in either of them resulting in the retention and degradation of both in the endoplasmic reticulum, thus reducing their transport to melanosomes.

• #1 An Overview of Albinism and Its Visual System Manifestations | Ento Key

  https://entokey.com/an-overview-of-albinism-and-its-visual-system-manifestations/

  The etiology of foveal hypoplasia in albinism is thought to be related to the decreased amount of melanin in the retinal pigment epithelium. […] The severity of the pigmentary dilution in OCA depends on the genetic subtype, constitutive (racial) pigmentation, and age of the patient. […] The ocular manifestations of patients with albinism vary in severity among the different types of this heterogeneous group of conditions but share characteristic common features. […] The optic nerve head may be grayish in patients with OCA1A, or it may be hypoplastic. […] Abnormal macular vascular patterns may be present in which retinal vessels course through the foveal avascular zone instead of arching around it, which is a hallmark of foveal hypoplasia. […] These abnormalities of decussation lead to a predominantly monocular representation of the central visual field in each occipital cortex. […] The abnormal transportation of tyrosinase in OCA4 disrupts the normal maturation process of the melanosomes.

• #1 Ocular albinism: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/ocular-albinism/

  Ocular albinism type 1 results from mutations in the GPR143 gene. This gene provides instructions for making a protein that plays a role in pigmentation of the eyes and skin. It helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision. […] Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally but mutations disrupt the protein’s function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism. […] Rare cases of ocular albinism are not caused by mutations in the GPR143 gene. In these cases, the genetic cause of the condition is often unknown.

• #1 Syndromic albinism: A review of genetics and phenotypes

  https://escholarship.org/uc/item/0fb7f671

  There are several syndromes of albinism associated with systemic pathology. These include Chediak-Higashi Syndrome (CHS), Hermansky-Pudlack Syndrome (HPS), Griscelli Syndrome (GS), Elejalde Syndrome (ES) and Cross-McKusick-Breen Syndrome (CMBS). […] Syndromic forms of albinism are associated with defects in the packaging of melanin and other cellular proteins. As such they are distinct from oculocutaneous albinism, which is associated with defects in the production of melanin (e.g., TRP1, P gene, and tyrosinase). […] The common etiologic element of these syndromes seems to involve defective formation of secretory vesicles and lysosomes. […] The relationship of albinism and the systemic manifestations that occur in HPS, GS, CHS and ES continues to be elucidated. The link appears to be related to the cellular machinery in the ribosome involved with vesicle and lysosome production and transport. Specifically, the link between immunodeficiencies and albinism involves the use of secretory vesicles and lysosomes by the immune system. […] Other secretory vesicles that relate to packaging of pigment are probably involved in hematological and neurological dysfunction of syndromic albinism, explaining why defects in these systems can manifest in syndromic albinism.

• #1 Masks of Albinism: Clinical Spectrum of Hermansky–Pudlak Syndrome

  https://www.mdpi.com/1422-0067/25/20/11260

  Hermansky–Pudlak syndrome (HPS) is a rare disease inherited in the autosomal recessive mode, including 11 clinical genetic subtypes. […] They are associated with impaired function of the BLOC protein complex (Biogenesis of Lysosome-related Organelles Complexes), and the subunits of the AP-3 complex (adaptor protein complex). […] The pathogenesis of HPS is primarily attributed to defects in the subunits of the AP-3 complex and biogenesis of the lysosome-related organelle (BLOC) complex. […] These complexes are crucial for the transport of endosomes (melanosomes, dense granules, Weibel–Palade bodies, and large dense granules) both to the extracellular space and between intracellular compartments. […] The differential involvement of these protein complexes in endosomal transport and biogenesis accounts for the varied clinical manifestations of HPS, both among different subtypes and between individual patients.

• #1 Albinism: Causes, Types, Pictures, Symptoms, and More

  https://www.healthline.com/health/albinism

  OCA3 is the result of a defect in the TYRP1 gene. […] OCA4 is caused by a defect in the SLC45A2 protein. […] Hermansky-Pudlak syndrome is a rare form of albinism that’s caused by a defect in one of 10 genes. […] Chediak-Higashi syndrome is another rare form of albinism that’s the result of a defect in the LYST gene. […] Griscelli syndrome is caused by a defect in one of three genes. […] The most accurate way to diagnose albinism is through genetic testing to detect defective genes related to albinism. […] Results from a small clinical trial (5 people) suggest that the drug nitisinone can help increase melanin in the skin and hair of people with OCA1b. More research is needed.

• #1

  https://www.aao.org/eye-health/diseases/what-is-albinism

  Albinism is caused by a genetic mutation that is usually passed from parents to child. The mutation disrupts the production of melanin, the pigment that protects the skin from UV rays. Melanin is also important for the proper development of the eye. Without melanin, the retina and the optic nerve may not develop properly. The retina (the light-sensitive tissue lining the back of the eye) and the optic nerve fibers help relay images to the brain. […] Albinism itself has no treatment. But some conditions that people with albinism have are treatable. Other conditions related to be albinism are manageable.

• #1 An Overview of Albinism and Its Visual System Manifestations | Ento Key

  https://entokey.com/an-overview-of-albinism-and-its-visual-system-manifestations/

  The term albinism (from albus, white) is applied to a group of inherited disorders that are characterized by decreased or absent melanin pigment in tissues, together with developmental abnormalities of the eye and visual pathways. […] In addition to decreased melanin in ocular tissues, patients with albinism have characteristic anatomical defects in the visual system, such as foveal hypoplasia and abnormal decussation of optic nerve fibers. […] All albino mammals have abnormalities of visual system development. Three main cellular disorders that lead to reduced vision have been identified: a reduction in the number of rod photoreceptors, the underdevelopment of the central retinal specialization or foveal hypoplasia, and a misrouting of some temporal retinal ganglion cell axons. […] Tyrosinase activity is required during some phases of the ipsilateral retinogeniculate pathway development.

• #1 Albinism – Wikipedia

  https://en.wikipedia.org/wiki/Albinism

  Besides the TYR gene, several other genes can cause albinism. […] Most forms of albinism follow a recessive pattern of inheritance. […] Albinism occurs throughout the animal kingdom. […] In mammals, albinism occurs once in every 10,000 births, but in birds, the rate is once in every 1,764 births. […] The absence of melanin results in abnormal development of eyes and leads to problems with focusing, and depth perception. […] Melanin protects the skin from ultra-violet radiation in sunlight. […] Albinism specifically affects the rod cells, but the number and distribution of the cones is unaffected. […] The lower survival rate of animals with albinism in certain environments has been documented, however, it has been stated that in studies where animals had many places to hide, predators captured albino and normally coloured animals at the same rate. […] Genetic studies of albinism in amphibians have focused on mutations in the tyrosinase gene.

• #1 Albinism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519018/

  In summary, complete absence or even partial melanin deficiency in utero leads to ocular structure malformation and optic tract misrouting and creates a multitude of irreversible intraocular (refractive) and extraocular (oculomotor or nonrefractive) problems. […] The genetic aberrations specific to each form of OCA, syndromic albinisms, and selected albinism-associated disorders are included below: […] Melanocytes number and distribution is preserved in the skin in patients with OCA, making melanoma a possible, albeit rare, a complication of albinism. […] Albinism has a broad range of presentations, and sometimes, hypomelanosis can only be considered in relation to the average pigmentation of other family members. […] Vision deficits are the major source of debility in non-syndromic albinism subjects. […] Squamous cell carcinomas are the most common malignancy in albinism, which can increase the relative risk as much as 1000 times.

• #1 Albinism and Other Genetic Disorders of Pigmentation | Plastic Surgery Key

  https://plasticsurgerykey.com/albinism-and-other-genetic-disorders-of-pigmentation/

  Albinism results from the dysfunction of a normal complement of pigment cells, which results in complete or partial loss of cutaneous pigmentation. […] The forms of albinism, including the subtypes of OCA as well as albinism syndromes with systemic manifestations, result either from enzymatic defects in the biosynthesis of melanin, from melanosomal defects that interfere with melanin formation, or from problems in the intracellular transport and localization of proteins essential for melanin biosynthesis. […] Awareness of the biologic basis of the distinction between congenital disorders of pigmentation, which are disorders of melanocyte development, and the varieties of albinism, which are disorders of melanocyte differentiation, is important for fully understanding their clinical manifestations.

• #1 Chat with our AI Assistant

  https://www.azolifesciences.com/article/Genetics-of-Albinism.aspx

  In 2013, a team of Chinese researchers reported the use of exome sequencing to reveal the molecular basis of albinism in an affected family. […] Further understanding of the pathological mechanisms that underlie syndromic and nonsyndromic OCA will allow comprehensive genetic screening and diagnosis to take place. […] Advancements in genetic research, including the identification of key genes and proteins involved in melanin biosynthesis, offer potential avenues for improved screening, diagnosis, and understanding of albinisms underlying mechanisms.

• #1 Clinical and genetic variability in children with partial albinism | Scientific Reports

  https://www.nature.com/articles/s41598-019-51768-8

  A recent report on the use of a panel-based sequencing approach in a large cohort of patients with albinism found that a definitive molecular diagnosis could be obtained in 72% of cases. […] Despite this recent progress in dissecting the molecular pathology of albinism, our understanding of the genetic basis of partial OCA remains incomplete. […] We identified four previously unreported disease-causing changes: two in SLC38A8, one in TYR and one in OCA2. […] In this cohort, TYR c.[575CA;1205GA] p.[(Ser192Tyr);(Arg402Gln)] was the most common pathogenic allele as it was suspected to be present in 7/12 patients. […] This haplotype has been found to lead to an additive decrease in tyrosinase function compared to each of the two variants individually. […] This recombination of common single polymorphisms that aberrantly affect protein function onto a single haplotype, with resulting significant decrease in protein function (in an additive or multiplicative fashion) to pathogenic levels is a rarely reported mechanism.

• #1 Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7 | bioRxiv

  https://www.biorxiv.org/content/10.1101/2025.02.04.636395v1

  Commander is an endosome associated sixteen protein assembly that associates with the sorting nexin 17 (SNX17) cargo adaptor to regulate cell surface recycling of internalised integral membrane proteins including integrins and lipoprotein receptors. […] We reveal how LRMDA mutations, causative for oculocutaneous albinism type 7 (OCA7), a hypopigmentation disorder accompanied by poor visual acuity, uncouple RAB32 and Commander binding thereby establishing the mechanistic basis of this disease. […] Our discovery and characterisation of this alternative Commander assembly establishes an unrecognised plasticity of Commander function within a highly complex organelle biogenesis pathway. This extends Commander function beyond the confines of SNX17-mediated cell surface recycling into RAB32-family mediated biogenesis of lysosome-related organelles and, potentially, other RAB32 regulated pathways including host-pathogen defence mechanisms.

• #1 CHOP Researchers Reveal Molecular Mechanism Behind Pigment Production in Skin Cells | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/chop-researchers-reveal-molecular-mechanism-behind-pigment-production-skin-cells

  The pigments that create skin, hair, and eye color are produced in organelles called melanosomes, which are located within skin cells called melanocytes and several types of eye pigment cells. Albinism, a condition characterized by an absence of pigment in the skin, hair and eyes, occurs when mutations within genes responsible for melanosome function or supporting cellular machinery prevent melanin pigments from being synthesized and stored. […] To better understand the mechanisms at play, researchers at Childrens Hospital of Philadelphia (CHOP) focused on BLOC-1, a protein complex required for the biogenesis and maturation of melanosomes and other lysosome-related organelles. BLOC-1 is composed of eight subunits, four of which are mutated in various forms of HPS, and is required to develop intracellular membrane tubes that allow melanin synthetic enzymes to be delivered to melanosomes. The researchers identified two lipid-modifying enzymes that are required for BLOC-1-dependent tube formation and thus for transporting melanin synthetic enzymes and other proteins into the melanosomes to generate pigment. The researchers found that these enzymes functioned sequentially and that depleting either enzyme resulted in reduced melanin content, emphasizing that both are required. […] This study showed us the what that two kinases are essential in melanosome biogenesis, and that these kinases localize sequentially.

• #1 A WHOLE EMBRYONIC SINGLE-CELL MODEL FOR OCULOCUTANEOUS ALBINISM TYPE II SUGGESTS A PH-SWITCHED TRANSCRIPTIONAL MECHANISM FOR KEY GENES REGULATING CELL FATE – Washington State University

  https://rex.libraries.wsu.edu/esploro/outputs/graduate/A-WHOLE-EMBRYONIC-SINGLE-CELL-MODEL-FOR/99901125038801842

  Oculocutaneous Albinism Type II (OCA2) is a non-syndromic pigment disorder associated with pathogenic variants of the OCA2 gene. OCA2 encodes a membrane-spanning active transport protein essential for pH regulation and substrate trafficking in melanosomes, the organelle in which the black pigment melanin is made. […] Using a novel zebrafish mutant as a disease model for OCA2 in humans, we have created the first whole-embryonic single cell transcriptomic atlas for this condition. The oca2 mutant zebrafish exhibits abnormal number and location of iridophores, an accessory pigment cell type found in fish and amphibians. This suggests that the oca2 protein or transcript is involved in the determination of non-melanocyte cell fate within the neural crest lineage, the transient population of multipotent stem cells from which pigment cells are derived.

• #1 What causes spontaneous eye movements in albinism?

  https://www.ophthalmologytimes.com/view/what-causes-spontaneous-eye-movements-in-albinism-

  Individuals with albinism often have poor vision and a new study from the Netherlands Institute for Neuroscience (NIN) reveals the underlying cause. […] According to the news release, one of the causes of vision issues in people with albinism is the spontaneous back-and-forth movement of the eye, called pendular nystagmus. […] Moreover, the researchers noted that understanding the underlying mechanisms behind this condition is essential for developing alternative treatment strategies. […] Jorrit Montijn, PhD, Valentina Rugiccini, and their colleagues, under the supervision of Alexander Heimel, PhD, have now demonstrated in albino mice that the cells in this brain area are no longer selective for the direction of image movement. […] The researchers noted the image cannot stabilize, leading to pendular nystagmus.

• #1 Multimodal phenotyping of foveal hypoplasia in albinism and albino-like conditions: a pediatric case series with adaptive optics insights | Scientific Reports

  https://www.nature.com/articles/s41598-024-66326-0

  The FAZ morphology is thought to be one of the main diagnostic clues in understanding the development of the foveal pit and the final foveal structure. […] A distinct FAZ has been reported as early as gestational age 25 weeks. […] While in the past it was thought that the FAZ was vascularized at some point, more convincing evidence suggests that it is always avascular during development. […] Moreover, recent evidence indicates that the identification of a FAZ could help distinguish between FH related to a disrupted development (i.e. oculocutaneous albinism), where the FAZ is absent, and FH related to retinal dystrophy (i.e. achromatopsia), where it is usually preserved. […] This study, although with a small number of patients, confirms that variants in TYR represent the most common causal association for FH, not only when FH is part of albinism but also when FH is clinically isolated.

• #1 Visual And Auditory Anomalies Associated With Albinism by Donnell J. Creel – Webvision

  https://webvision.med.utah.edu/book/electrophysiology/visual-and-auditory-anomalies-associated-with-albinism/

  C. L. Sheridan (1965) compared the interocular visual pathways in split brain ocularly pigmented (hooded) rats and albino rats. Sheridan concluded Perhaps the paucity of uncrossed fibers that characterized rodents in general is even further reduced in the albino. That year Lund (1965) verified Sheridans hypothesis anatomically. Lund stated albino rats display no organized uncrossed optic fibers. Lund agreed with previous estimates that pigmented rats possess up to 10% uncrossed optic fibers. […] Many animal studies in the 1970s reported that all albino mammals with oculocutaneous, or only ocular albinism, demonstrate reduced uncrossed optic projections (Sanderson et al., 1975; Creel Giolli, 1976; Guillery et al., 1979). […] The organization of the visual system varies considerably among mammals. Haplorrhine primates display well-defined foveae, foveal avascular zone, and large numbers of uncrossed optic fibers, whereas rodents and even carnivores exhibit only a central fixation area in the retina.

• #1 Albinism and Human Eyes: How Does Albinism Affect Vision?

  https://www.allaboutvision.com/conditions/related/how-albinism-affects-vision/

  Ocular albinism affects only the eyes, not the skin or hair. Ocular albinism reduces coloring in the iris and affects proper development of the retina. […] People with OA may have light sensitivity, nystagmus, strabismus and depth perception issues. Their visual acuity is typically lower than normal, ranging from 20/60 to 20/400. […] The ability to mimic OCA using a cell model is an important breakthrough. It will lead to a greater understanding of how albinism leads to abnormal development of the retina, optic nerve (which carries visual signals to the brain) and fovea (the area in the retina responsible for our sharpest central vision). […] This could lead to greatly improved visual acuity in people with OCA.

• #2 Albinism: Types, Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/21747-albinism

  Albinism is a rare genetic condition caused by mutations, or changes, of certain genes that affect the amount of melanin your body produces. […] Variations in the genes responsible for melanin production cause albinism. Specific genes associated with oculocutaneous albinism include: TYR, OCA2, TYRP1, SLC45A2. […] Variations in the GPR143 gene are associated with ocular albinism. […] Oculocutaneous albinism (OCA) follows an autosomal recessive pattern of inheritance. This means you must inherit an albinism gene from both of your biological parents to develop the condition yourself. […] Ocular albinism (OA) usually follows an X-linked pattern of inheritance. This means the genetic variation is passed through the X chromosome. OA mostly occurs in males.

• #2 Albinism: for patients – Gene Vision

  https://gene.vision/knowledge-base/albinism-for-patients/

  Albinism is an inherited condition that affects approximately 1 in 5,000 to 1 in 17,000 people. It is caused by mutations in one of 18 genes that leads to reduced or no production of melanin, a pigment which determines the colour of our skin, hair, and eyes. […] Oculocutaneous albinism is caused by changes in 18 genes coding for proteins that help with melanin production and transport of melanosomes (a structure in the cell that synthesise, store and transport melanin). As a result, there is little or no pigment present in the skin, hair, and eyes, as well as poor vision due to the abnormal development of the structures in the eye. Ocular albinism differs from oculocutaneous albinism as it has minimal skin and hair involvement and is caused by mutations in a single gene called GPR143, which is involved in a pathway that controls the growth and maturation of melanosomes. […] The severity of the various symptoms associated with albinism is dependent on the extent of melanin deficiency.

• #2 Albinism: What it is, types, symptoms, treatment, and is it genetic

  https://www.medicalnewstoday.com/articles/245861

  Albinism is an inherited disease characterized by a substantially lower rate of melanin production. […] If there is a change in one of these genes, it can cause albinism. Experts estimate that 1 in 70 people carry these genes. […] Most commonly, the mutations interfere with an enzyme called tyrosinase. This enzyme breaks down the amino acid tyrosine and creates melanin. […] Depending on the specific mutation, melanin production either slows down or stops entirely. […] As melanin plays a vital role in retinal and optic nerve development, these genetic changes cause visual problems. […] Yes, albinism is genetic. Most types of albinism have what doctors call an autosomal recessive inheritance pattern. […] With autosomal recessive inheritance, an individual must receive mutated copies of a gene from both the mother and father to develop albinism.

• #2 Ocular albinism: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/ocular-albinism/

  Ocular albinism type 1 results from mutations in the GPR143 gene. This gene provides instructions for making a protein that plays a role in pigmentation of the eyes and skin. It helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision. […] Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally but mutations disrupt the protein’s function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism. […] Rare cases of ocular albinism are not caused by mutations in the GPR143 gene. In these cases, the genetic cause of the condition is often unknown.

• #2 Albinism: Causes, Types, Pictures, Symptoms, and More

  https://www.healthline.com/health/albinism

  OCA3 is the result of a defect in the TYRP1 gene. […] OCA4 is caused by a defect in the SLC45A2 protein. […] Hermansky-Pudlak syndrome is a rare form of albinism that’s caused by a defect in one of 10 genes. […] Chediak-Higashi syndrome is another rare form of albinism that’s the result of a defect in the LYST gene. […] Griscelli syndrome is caused by a defect in one of three genes. […] The most accurate way to diagnose albinism is through genetic testing to detect defective genes related to albinism. […] Results from a small clinical trial (5 people) suggest that the drug nitisinone can help increase melanin in the skin and hair of people with OCA1b. More research is needed.

• #2 Albinism: for professionals – Gene Vision

  https://gene.vision/knowledge-base/albinism-for-doctors/

  Pathogenic mutations in 18 genes have been identified to cause OCA (syndromic/non-syndromic) or OA by affecting melanin biosynthesis or melanin distribution in dermal tissues. […] Melanin is synthesised from an organelle called melanosomes which are located inside melanocytes. Melanocytes are derived from the neural crest ectoderm during embryonic development and migrate into the skin, hair, eyes and inner ear to fulfil their primary function. Melanogenesis is tightly regulated by the activity of tyrosinase. It converts L-tyrosine to L-DOPA or dopaquinone for the production of eumelanin (brown to black colour) or pheomelanin (red to yellow colour), two common forms of melanin in humans. […] Apart from its role in protecting the skin from harmful ultraviolet (UV) rays, melanin is also crucial to the development of ocular structures and neural pathways. It induces the formation of fovea, optic nerves, optic tracts and visual cortex, along with triggering the crossover of optic nerve fibres from each eye at the chiasm to the contralateral occipital lobe, which is essential for binocular vision.

• #2 Oculocutaneous albinism | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-43

  Oculocutaneous albinism (OCA) is a group of inherited disorders of melanin biosynthesis characterized by a generalized reduction in pigmentation of hair, skin and eyes. […] Oculocutaneous albinism (OCA) is a group of four autosomal recessive disorders caused by either a complete lack or a reduction of melanin biosynthesis in the melanocytes resulting in hypopigmentation of the hair, skin and eyes. Reduction of melanin in the eyes results in reduced visual acuity caused by foveal hypoplasia and misrouting of the optic nerve fibres. […] OCA is a group of congenital heterogeneous disorders of melanin biosynthesis in the melanocytes. At least four genes are responsible for the different types of OCA (OCA1-4). Most patients are compound heterozygotes, i.e. harbouring two different mutations in one of the genes.

• #2 Albinism – Wikipedia

  https://en.wikipedia.org/wiki/Albinism

  Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and reddish pink or blue eyes. […] By definition albinism is a genetic condition, however a similar coloration could be caused by diet, living conditions, age, disease, or injury. […] Oculocutaneous albinism (OCA) is a clearly defined set of seven types of genetic mutations which reduce or completely prevent the synthesis of eumelanin or pheomelanin, resulting in reduced pigmentation. […] The production of melanin occurs in melanocytes in a complex process involving the enzyme tyrosinase. […] Mammals have a gene that codes for the presence of tyrosinase in cells called the TYR gene. If this gene is altered or damaged, melanin cannot be reliably produced and the mammal becomes an albino.

• #2 Germline and somatic albinism variants in amelanotic/hypomelanotic melanoma: Increased carriage of TYR and OCA2 variants | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238529

  Common variants in several of these genes are associated with normal as well as pathological variation in human pigmentation. An important example is OCA2, where protein coding or regulatory variants alter the expression or function of the P-protein, which assists trafficking and processing of the TYR protein. […] Rare deleterious variants in TYR/OCA1 were more common in amelanotic/hypomelanotic melanoma cases than pigmented melanoma cases. The OCA2 hypomorphic allele p.V443I was more common in melanoma cases than controls, and more so in amelanotic/hypomelanotic melanoma. […] Variants in TYR and OCA2 may play a role in amelanotic/hypomelanotic melanoma susceptibility. We suggest that somatic loss of function at these loci could contribute to the loss of tumor pigmentation. […] These results clearly demonstrate that rare albinism-associated variants in TYR, and the OCA2 p.V443I variant, are more frequent in individuals with melanoma as compared to controls.

• #2 Oculocutaneous albinism | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-43

  OCA1 (MIM 203100) is caused by mutations in the tyrosinase gene (TYR, MIM 606933) on chromosome 11q14.3. […] Mutations in the OCA2 gene (formerly known as the P-gene) (MIM 203200) cause the OCA2 phenotype. […] OCA3 (MIM 203290) is caused by mutations in tyrosinase-related protein 1 (TYRP1, MIM 115501, 9p23). […] Mutations in the membrane-associated transporter protein gene (MATP, also known as SLC45A2, MIM 606202) cause OCA4 (MIM 606574).

• #2 Information Bulletin – Ocular Albinism – National Organization for Albinism and Hypopigmentation

  https://albinism.org/information-bulletin-ocular-albinism/

  Ocular Albinism (also known as OA1 or Nettleship-Falls Ocular Albinism) is an X-linked recessive condition that results from the mutation of the GPR143 gene and is usually associated with less than normal visual acuity. The GPR143 gene creates a signaling protein that plays a key role in the development of the eye. […] The reduced presence of pigment affects the ocular system for people with OA in several ways, although exactly why these changes occur are not fully understood. […] The center parts of the retina that are responsible for detailed vision (macula and fovea) have reduced amount of pigment, which means less light information is transmitted from the retina to the brain. […] Although it is not understood why, it is well-established that the nerve fibers do not follow the same routes into and through the brain as they do in an individual without albinism. […] Ocular albinism is an X-linked condition as there is only one gene, GPR143, that can cause the condition. The GPR143 gene is located on the X chromosome. […] The only way to diagnose OA accurately is a genetic test, confirming a pathogenic variant in the GPR143 gene.

• #2 Albinism – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/albinism/symptoms-causes/syc-20369184

  Albinism related to rare hereditary syndromes can occur. For example, Hermansky-Pudlak syndrome includes a form of OCA, as well as bleeding and bruising problems and lung and bowel diseases. Chediak-Higashi syndrome includes a form of OCA, as well as immune problems with recurrent infections, problems with the brain and nerves, bleeding disorders, and other serious issues.

• #2 Hermansky-Pudlak syndrome – UpToDate

  https://www.uptodate.com/contents/hermansky-pudlak-syndrome

  Hermansky-Pudlak syndrome (HPS) is caused by homozygous or compound heterozygous mutations in 1 of 11 genes that encode components in one of four HPS protein-associated complexes: adapter protein 3 (AP-3) and biogenesis of lysosome-related organelles complex 1, 2, and 3 (BLOC-1, BLOC-2, and BLOC-3). All four complexes support intracellular biogenesis, trafficking, and homeostasis of lysosome or lysosome-related organelles (LROS) (table 1) [1,8,9]. […] The hypopigmentation in HPS is secondary to impaired melanosome formation, trafficking, or transfer to keratinocytes, while the melanin biosynthesis in melanocytes is unaffected [8]. Immature and abnormal melanosomes cause reduced pigmentation of hair, skin, and eyes. In contrast, oculocutaneous albinism is caused by mutations in genes encoding proteins involved in the melanin biosynthesis pathway.

• #2 Albinism: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1200472-overview

  The term albinism originates from the word, albus (Latin for white), and it is an inherited disorder characterized by reduced pigmentation. Albinism is caused by pathogenic variants in genes important for melanin synthesis. […] The melanin pathway consists of a series of reactions that converts tyrosine into 2 types of melanin: 1) black-brown eumelanin and 2) red-blond pheomelanin. Genetic variants affecting proteins/enzymes along this pathway inevitably result in reduced melanin production. […] The development of the ocular system is highly dependent on the presence of melanin. Absent or decreased melanin can cause abnormal crisscrossing of optic nerve fibers as a result of misdirected retinogeniculate projections. Melanin is believed to control neuronal target specificity in the brain. In cases of incomplete pigmentation, the developing optic tracts almost entirely intersect at the chiasm, whereas in individuals without albinism, almost half (45%) of axons beginning in the temporal half of the retina pass through the chiasm uncrossed and project to the same-sided lateral geniculate nucleus. […] This results in predominantly monocular vision and reduced binocular depth perception.

• #2 An Overview of Albinism and Its Visual System Manifestations | Ento Key

  https://entokey.com/an-overview-of-albinism-and-its-visual-system-manifestations/

  The term albinism (from albus, white) is applied to a group of inherited disorders that are characterized by decreased or absent melanin pigment in tissues, together with developmental abnormalities of the eye and visual pathways. […] In addition to decreased melanin in ocular tissues, patients with albinism have characteristic anatomical defects in the visual system, such as foveal hypoplasia and abnormal decussation of optic nerve fibers. […] All albino mammals have abnormalities of visual system development. Three main cellular disorders that lead to reduced vision have been identified: a reduction in the number of rod photoreceptors, the underdevelopment of the central retinal specialization or foveal hypoplasia, and a misrouting of some temporal retinal ganglion cell axons. […] Tyrosinase activity is required during some phases of the ipsilateral retinogeniculate pathway development.

• #2 Visual And Auditory Anomalies Associated With Albinism by Donnell J. Creel – Webvision

  https://webvision.med.utah.edu/book/electrophysiology/visual-and-auditory-anomalies-associated-with-albinism/

  C. L. Sheridan (1965) compared the interocular visual pathways in split brain ocularly pigmented (hooded) rats and albino rats. Sheridan concluded Perhaps the paucity of uncrossed fibers that characterized rodents in general is even further reduced in the albino. That year Lund (1965) verified Sheridans hypothesis anatomically. Lund stated albino rats display no organized uncrossed optic fibers. Lund agreed with previous estimates that pigmented rats possess up to 10% uncrossed optic fibers. […] Many animal studies in the 1970s reported that all albino mammals with oculocutaneous, or only ocular albinism, demonstrate reduced uncrossed optic projections (Sanderson et al., 1975; Creel Giolli, 1976; Guillery et al., 1979). […] The organization of the visual system varies considerably among mammals. Haplorrhine primates display well-defined foveae, foveal avascular zone, and large numbers of uncrossed optic fibers, whereas rodents and even carnivores exhibit only a central fixation area in the retina.

• #2

  https://dermnetnz.org/topics/albinism

  Albinism is mostly a recessively inherited disease, which means two albinism genes are inherited (one from each parent). […] The main problems of albinism are caused by the inability of the body to produce melanin pigment (whose major role in the skin is to absorb UV light from the sun so skin is not sun-damaged). It also has a role in the development of normal vision of the eye. […] Having white or light coloured hair due to lack of melanin is no cause for concern, however, lack of melanin in the skin and eyes can cause the following problems: […] Impaired vision: although not blind, vision is impaired and may not be fully corrected with glasses. Varying degrees of near-sightedness or far-sightedness exist. […] Retinal involvement: this is an important area of the eye as it is responsible for sending signals to the brain. Impaired transmission of signals causes various vision disorders.

• #2 Albinism pathophysiology – wikidoc

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

  Melanocytes are derived from neural crest ectoderm and are found in hair follicles, skin, eyes, and inner ear. […] Mutation in Tyrosinase enzyme is responsible for causing albinism. […] Tyrosinase mutation is seen in oculocutaneous albinism 1 (OCA1) and autosomal-recessive ocular albinism (AROA). […] Lack of melanin increase chances of sun-damage related diseases including actinic keratosis and UV-related malignancies. […] In albinism, most of nerve fibers decussate at optic chiasm and cause monocluar vision. […] In albinism, macular pigment is absent and fovea hypoplasia leads to decreased visual acuity.

• #2 Clinical and genetic variability in children with partial albinism | Scientific Reports

  https://www.nature.com/articles/s41598-019-51768-8

  Individuals who have ocular features of albinism and skin pigmentation in keeping with their familial background present a considerable diagnostic challenge. […] A definitive molecular diagnosis was made in 8/12 probands (67%) and a possible molecular diagnosis was identified in a further 3/12 probands (25%). […] A disease-causing TYR haplotype comprised of two common, functional polymorphisms, TYR c.[575CA;1205GA] p.[(Ser192Tyr);(Arg402Gln)], was found to be particularly prevalent. […] Overall, our findings highlight that panel-based genetic testing is a clinically useful test with a high diagnostic yield in children with partial/ocular albinism. […] Albinism, and OCA in particular, exhibits significant clinical and genetic heterogeneity. […] The use of genetic testing early in the care pathway offers significant potential for accelerating diagnosis in individuals suspected to have partial OCA.

• #2 Clinical and genetic variability in children with partial albinism | Scientific Reports

  https://www.nature.com/articles/s41598-019-51768-8

  We identified two individuals with partial albinism that were homozygous for the TYR p.[(Ser192Tyr);(Arg402Gln)] allele. […] We identified two individuals with partial albinism and monoallelic rare variants in both TYR and OCA2 a significant enrichment compared to a control cohort from the 100,000 genomes project pilot dataset. […] However, convincing evidence is yet to be reported in the scientific literature.

• #2 A WHOLE EMBRYONIC SINGLE-CELL MODEL FOR OCULOCUTANEOUS ALBINISM TYPE II SUGGESTS A PH-SWITCHED TRANSCRIPTIONAL MECHANISM FOR KEY GENES REGULATING CELL FATE – Washington State University

  https://rex.libraries.wsu.edu/esploro/outputs/graduate/A-WHOLE-EMBRYONIC-SINGLE-CELL-MODEL-FOR/99901125038801842

  Single cell transcriptomic analysis of the mutant revealed alterations of several gene networks involved in neural crest differentiation and specification. Notably, acp1 and ctnnb1/2 exhibited significant negative log fold change values in the neural crest. acp1, a protein tyrosine phosphatase involved in melanogenesis, is also a positive effector for transcription of beta catenin (ctnnb1/2). […] Beta catenin-dependent pathways Notch and Wnt were obstructed in neural crest, neural plate, and optic nerve cell populations, consistent with downstream abnormalities to non-melanocyte cell fate and number observed in the oca2 mutant. […] Transcription of acp1 is also known to be strongly inhibited by increases in extracellular pH. Based on this information we propose that oca2 prevents pH-dependent repression of acp1 transcription by maintaining the intracellular H+ gradient.

• #2 What causes spontaneous eye movements in albinism?

  https://www.ophthalmologytimes.com/view/what-causes-spontaneous-eye-movements-in-albinism-

  According to Montijn, the researchers have demonstrated that the nucleus of the optic tract might be the source of the problem. […] Previous research already suggested that this area is involved in eye movements, but it could not be ruled out that (also) other areas, such as the cortex, cause pendular nystagmus, he said in the news release. […] Montijn also pointed out the researchers do know there is something wrong with this area, but they still don’t know what can be done about it.

• #2 Multimodal phenotyping of foveal hypoplasia in albinism and albino-like conditions: a pediatric case series with adaptive optics insights | Scientific Reports

  https://www.nature.com/articles/s41598-024-66326-0

  This observation has limitation since melanin is also present in the choroid and the RPE. […] Since it is well known that in syndromic and non-syndromic forms of albinism the retinal pigmentation pathway is altered, one may argue that adaptive optics imaging could have the potential to investigate the abnormal distribution of retinal pigmentation allowing new insight into pathogenic mechanisms of disrupted embryogenesis in albinos and albino-like phenotypes. […] In conclusion, our study reinforces the potential of new imaging techniques like adaptive optics and of genomic technologies to improve understanding of apparently isolated foveal hypoplasia.

• #2 What causes spontaneous eye movements in albinism?

  https://www.ophthalmologytimes.com/view/what-causes-spontaneous-eye-movements-in-albinism-

  Individuals with albinism often have poor vision and a new study from the Netherlands Institute for Neuroscience (NIN) reveals the underlying cause. […] According to the news release, one of the causes of vision issues in people with albinism is the spontaneous back-and-forth movement of the eye, called pendular nystagmus. […] Moreover, the researchers noted that understanding the underlying mechanisms behind this condition is essential for developing alternative treatment strategies. […] Jorrit Montijn, PhD, Valentina Rugiccini, and their colleagues, under the supervision of Alexander Heimel, PhD, have now demonstrated in albino mice that the cells in this brain area are no longer selective for the direction of image movement. […] The researchers noted the image cannot stabilize, leading to pendular nystagmus.

• #2

  https://www.aao.org/eye-health/diseases/what-is-albinism

  Albinism is caused by a genetic mutation that is usually passed from parents to child. The mutation disrupts the production of melanin, the pigment that protects the skin from UV rays. Melanin is also important for the proper development of the eye. Without melanin, the retina and the optic nerve may not develop properly. The retina (the light-sensitive tissue lining the back of the eye) and the optic nerve fibers help relay images to the brain. […] Albinism itself has no treatment. But some conditions that people with albinism have are treatable. Other conditions related to be albinism are manageable.

• #3 Oculocutaneous albinism: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/oculocutaneous-albinism/

  Oculocutaneous albinism can result from variants (also known as mutations) in several genes, including TYR, OCA2, TYRP1, and SLC45A2. Variants in the TYR gene cause type 1, variants in the OCA2 gene cause type 2, variants in the TYRP1 gene cause type 3, and variants in the SLC45A2 gene cause type 4. Variants in additional genes likely underlie the other forms of this disorder. The genes associated with oculocutaneous albinism are involved in producing a pigment called melanin, which is the substance that gives skin, hair, and eyes their color. […] Variants in any of these genes disrupt the ability of cells to make melanin, which reduces pigmentation in the skin, hair, and eyes. A lack of melanin in the retina leads to the vision problems characteristic of oculocutaneous albinism. […] Some individuals with oculocutaneous albinism do not have variants in any of the known associated genes. In these people, the genetic cause of the condition is unknown.

• #3 Albinism: for professionals – Gene Vision

  https://gene.vision/knowledge-base/albinism-for-doctors/

  Pathogenic mutations in 18 genes have been identified to cause OCA (syndromic/non-syndromic) or OA by affecting melanin biosynthesis or melanin distribution in dermal tissues. […] Melanin is synthesised from an organelle called melanosomes which are located inside melanocytes. Melanocytes are derived from the neural crest ectoderm during embryonic development and migrate into the skin, hair, eyes and inner ear to fulfil their primary function. Melanogenesis is tightly regulated by the activity of tyrosinase. It converts L-tyrosine to L-DOPA or dopaquinone for the production of eumelanin (brown to black colour) or pheomelanin (red to yellow colour), two common forms of melanin in humans. […] Apart from its role in protecting the skin from harmful ultraviolet (UV) rays, melanin is also crucial to the development of ocular structures and neural pathways. It induces the formation of fovea, optic nerves, optic tracts and visual cortex, along with triggering the crossover of optic nerve fibres from each eye at the chiasm to the contralateral occipital lobe, which is essential for binocular vision.

Zobacz więcej