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The Pedigree Below Shows the Transmission of Albinism (Absence of Skin Pigment) in a Human Family.

Written By quarta-feira, 9 de março de 2022 Add Comment Edit

Chrysavgi Adamopoulou, Md, Leo A. Kim, MD, PhD, Koushik Tripathy, Doctor (AIIMS), FRCS (Glasgow), Neelakshi Bhagat, MD, FACS, Anjali K. Pathak, Chiliad.D., Jennifer I Lim MD, Yasser G. Elshatory, Physician, Jenna May Kim, MD

Assigned condition Up to Appointment

 by Neelakshi Bhagat, Physician, FACS on Nov 2, 2021.


Originating from the Latin word "albus" [1] meaning white, albinism represents a set of inherited conditions characterized past absent or decreased tissue melanin in conjunction with characteristic ocular and visual pathway anomalies. Those affected past this condition manifest varying degrees of hypopigmentation and vision-related inability. These atmospheric condition generally are incurable merely are static. Proper ophthalmic and dermatologic management may be crucial in maximizing visual potential and overall prognosis. Genetic counseling for the affected individuals and their families is recommended.

Illness Entity and Epidemiology

Albinism refers to reduced pigmentation compared to others of the aforementioned racial background, with characteristic middle involvement. All races of the human species can be affected, although the phenotype is more recognizable in night-skinned individuals. The disorder tin exist divided into ii groups: oculocutaneous albinism (OCA)-—the well-nigh common status among hypopigmentation disorders [2]--with varying degrees of involvement of the eyes, hair, and skin; the second group is the less common group called ocular albinism (OA) with affliction involvement limited to the eyes. These heterogeneous groups of the relatively rare genetic condition affecting the tyrosine/melanin biochemical cascade are estimated to occur worldwide at a range of 1 in 5,000 to 1 in 40,000 (nigh 1 in 37,000 in America)[three] [4]. In certain localities in Africa, however, the prevalence is estimated to be as high every bit 1 in i,000 possibly as a issue of consanguinity, and is a notable regional public wellness outcome [4] [5] [6].

Clinical Features

A number of features in combination paint the picture of albinism.

OCT of a patient with albinism showing foveal hypoplasia

  • Iris transillumination: The iris in albinism has lilliputian to no pigment to screen out devious light coming into the eye. On slit lamp exam, the examiner may notice speckled or diffuse transillumination defect. This finding, while common with albinism, is not specific as iris transillumination occurs in diseases unrelated to albinism such as pseudoexfoliation, pigment dispersion syndrome, megalocornea, iris atrophy, and Axenfeld-Rieger spectrum [7]. When nowadays in an otherwise normal individual, this finding may betoken carrier status of a hypomelanotic gene mutation.
    The iris may be translucent and the margin of the crystalline lens may be visible on transillumunation during slit lamp examination.
  • Pendular nystagmus: Nystagmus refers to rhythmic, involuntary, conjugate eye motility. Affected infants may take large aamplitude with low frequency pattern of eye motion starting at 2-iii months of age, later changing to a pendular form without singled-out fast or ho-hum phases. Eye muscle surgery may be considered to reduce nystagmus.
  • Foveal hypoplasia (absence of a foveal pit): In albinism, the retina does not develop unremarkably earlier birth and in infancy because of inappropriate retinal pigment epithelium (RPE) pigmentation that is required for macular evolution. Optical coherence tomography (OCT) tin demonstrate an absence of the foveal pit and the loss of normal thinning of the retina. Besides, the foveal avascular zone is small or nonexistent with vessels crossing the area two disc diameter temporal to the optic disc margin. Foveal hypoplasia is the single most important contributor to poor vision in albino patients. [vii]
  • Abnormal decussation of the visual pathways: Usually about one-half of optic nerve fibers from each heart decussates at the optic chiasm to the contralateral side, contributing to stereopsis. Albinism is associated with fiber over-decussation, resulting in crossing of up to 90% of fibers to the contralateral side and thus strabismus and loss of stereopsis. Evidence of this aberration tin can exist detected by iii-lead visual evoked potential (VEP) for proper counseling regarding visual potential of a patient.
  • Strabismus: Misalignment of the optics and related anomalous head tilt tin can occur in association with albinism. Kumar et al reported that the strabismus is seen in higher proportions of those with albinism compared to those with idiopathic infantile nystagmus, suggesting different mechanisms underlying the cause of strabismus in the 2 disorders. [8]
  • Photophobia: Sensitivity to vivid light and glare can occur due to scattering of light inside the eye. Patients may prefer to article of clothing sunglasses to reduce their sensitivity to low-cal.
  • Refractive Errors: Both myopia and hyperopia can occur, and astigmatism is very mutual.
  • Poor vision: Vision can range from normal for those minimally afflicted to legal incomprehension or worse (vision less than 20/200) for those with more than severe forms of albinism. Near vision is often ameliorate than distance vision. By and large, those who have the least amount of pigment (i.e. near severely afflicted) have the poorest vision.

Color fundus photographs of a patient with albinism. Blunted foveal light reflex suggests hyplasia of the fovea bilaterally.

Slit lamp photographs of a patient with albinism showing lite colored eye lashes and near-complete iris transillumination.

Etiology

Biochemical pathway leading to melanin product. Notation that Tyrosinase is essential for the first ii steps of the pathway.

Oculocutaneous albinism is a group of autosomal recessive conditions associated with mutations in several enzymes or membrane proteins that contribute to melanin synthesis. The phenotype arises from a problem of melanocyte differentiation that renders synthesis or ship of melanin dysfunctional within the cells. Considering the color of both skin and iris are adamant by the size and number of melanosomes (organelles that comprise melanin), any defect in melanin production or transport of melanosomes (intracellular vesicles that store melanin) affects skin and irig pigmentation. The phenotype in albinism depends on whether or not remainder enzyme activeness is present.  Reduced tyrosinase activity will confer the power to larn pigmentation in pare, pilus (white pilus at birth may get blonde  or cherry-red dark-brown, and skin may tan), whereas patients having no tyrosinase activity will have white pilus and white skin throughout their lifetime. Similarly iris color tends to fall on the spectrum from very calorie-free blue to light hazel.  The severity of a patient's visual function are often dependent on the degree of nystagmus and amount of pigmentation; hence, patients with no tyrosinase action (tyrosinase-negative oculocutaneous albinism) accept poorer visual.  Ocular albinism is distinguished from oculocutaneous albinism by less of pare and pilus involvement, an Ten-linked recessive inheritance pattern, and the mutation in a singled-out loci (GPR143) whose gene product is required for melanosomal maturation. A full of fifteen genes are currently associated with diverse types of albinism[nine] with every bit many as 729 mutations reported in the Human Gene Mutation Database associated with any of those loci[10].

Genetic Classification

Albinism has classically been organized into two broad categories, tyrosinase-positive (mild to moderate) and tyrosinas-negative (astringent) albinism, based on one'south phenotype rather than on genotype. With evolution of molecular genetics, finer classification according to the afflicted cistron has dictated nomenclature of the subtypes.

At that place are at present 7 types of OCA not including the syndromes with systemic manifestations (see Differential diagnoses). All seven types are inherited in an autosomal recessive mode and are thus found in both males and females, which is in dissimilarity to that of 10-linked recessive inheritance of ocular albinism (see below). Ocular nystagmus is seen in virtually all forms of OCA[11].

OCA Type 1

This type, generally known equally tyrosinase-related OCA, constitutes several subtypes that occur due to mutation in TYR cistron for tyrosinase (chromosome 11q14-q21)[12]. Tyrosinase enzyme catalyzes the starting time ii steps in the melanin biosynthesis pathway, responsible for converting tyrosine to DOPA and after to DOPAquinone. Depending on differential production of the end product melanin, the severity of phenotype varies. A point mutation of TYR drives the conformation of the enzyme, which results in either absent or decreased enzyme action. Nearly 200 mutations in TYR are known to date.

  • OCA 1A was formerly known as "tyrosinase-negative" albinism due characteristic absence of all pigmentation [13]. Patients affected by OCA 1A thus take the nigh profound phenotype of all OCAs with the greatest hazard for skin cancer and highest frequency of visual symptoms and vigil loss. Hair bulbs of the affected individuals remain DOPA-negative throughout their lives, indicating that the tyrosinase activity is fully inactive (come across OCA 1MP for comparison)[14]. Due to the relative severity of ocular and dermatologic problems, close ophthalmic and dermatologic care is essential.
  • OCA 1B was known as the "yellow variant" due to reduced, but not absent-minded, tyrosinase activity that produce some pigment. Patients with 1B may be indistinguishable from 1A at nascency due to lack of any detectable pigment early on [vii], but during the offset several years of life 1B patients accumulate yellow pigment in their skin, eye, and pilus. Their vision is moderately to severely reduced.
  • OCA 1MP stands for "OCA 1 Mimal Pigment." King et al in 1986[15] get-go proposed OCA minimal pigment as a subtype of OCA 1 past showing matted TYR activity and clinically detectable accumulation of pigment only in the irises that increases with age. The most recent update of the definition proposed past Kono et al[16] claimed that the sites of pigment accumulation include pilus and lentigo. With life-long negative DOPA staining of hair bulbs, nevertheless, 1MP phenotype contrasts with OCA 1B that has positive DOPA staining.
  • OCA 1 TS is the Temperature Sensitive form that earned its name from variable tyrosinase activity depending on skin temperature. In this subtype, tyrosinase activeness is inversely proportional to temperature, leading to nighttime hair on the cooler extremities merely white hairs near the body core such as the axilla, pubic area, and scalp. Equally in OCA 1B, the patients tin can be duplicate at birth from OCA 1A[vii].

OCA Type 2

OCA blazon ii is the well-nigh common blazon of albinism throughout the world with the highest frequency in equatorial Africa [2]. The characteristic cistron involvement for OCA2 is the OCA2 gene, previously known as P factor. OCA2 is responsible for melanosome function every bit information technology helps regulate the influx of tyrosine and other internal surround of the melanosome thus affecting the functionality of the organelle and melanin production. Of notation, non-pathologic polymorphisms of the OCA2 contribute to iris colors in normal individuals [7]. This disorder is by and large a milder form of OCA type one, with cutaneous pigmentation ranging from white to fair; hair color ranging from yellow to even black; and generally milder visual dysfunction compared to OCA ane. At times the affected individual may be indistinguishable from having OCA 1B and OCA 1MP[17]. Interestingly, virtually 1% of patients with either Prader-Willi or Angelman syndrome are hypopigmented though often without ocular features of albinism. This miracle is due to the position of the OCA2 between the genes whose deletions are responsible for the ii syndromes[18] [nineteen].

  • OCA 2 Brown Albinism (BOCA) is a part of the clinical spectrum of OCA2. This variant of OCA 2 was initially identified in Africans of Nigerian and Ghanan beginnings and in and African Americans with lite brown pilus and skin[20] [21] . OCA 2 patients tin present anywhere between the classic phenotype (yellow/blond hair, creamy skin, blueish/hazel irides) to brown-pigmentation. Afflicted individuals from other ethnic groups can take moderate to nearly-normal cutaneous pigmentation [21] [22] [23].

OCA Blazon 3

OCA 3 occurs due to a mutation in TYRP1 (tyrosinase-related poly peptide) factor. This subtype of OCA is seen in African-born blacks merely rarely in other ethnicities [24] [25]. Phenotypes overlap with BOCA (come across above, OCA ii) and with red/rufous OCA (ROCA) [26] [7], although as the phenotype names imply, the BOCA can be differentiated from ROCA based on skin and pilus color. ROCA phenotype is characterized by red-bronze skin color, ginger hair, and blue or brownish irides [27]. Studies take since shown that TYRP1 contributes to melanin synthesis too as melanocyte proliferation and apoptosis [28].

OCA Type four

Recessive mutation in membrane-associated transport protein factor (MATP), as well known every bit SLC45A2 , is responsible for OCA type 4. Although the gene was offset identified in a Turkish patient [29], information technology has since been found in albino subjects in Japan and elsewhere in Europe as well. This is the tertiary near common blazon of OCA later on OCA2 and OCA1 [9].

OCA Type 5

A new OCA gene chosen OCA5 was found to be responsible for the typical OCA phenotype in a consanguinous Pakistani family[30]. This factor is mapped onto chromosome 4q24 and the genotype was designated OCA 5. Further studies on this gene are underway.

OCA Type 6

In 2013, a Chinese grouping of researchers, Wei et al [31] plant mutations in SLC24A5 on 15q21.1 among patients of Chinese origin who presented with characteristic phenotype of non-syndromic OCA. This gene, previously studied but not linked straight to OCA phenotype, is believed to impair or disrupt melanosomal maturation [32]. OCA due to mutation in SLC24A5 gene has been since termed OCA type 6. Morice-Picard et al have since shown that this mutation is seen in different ethnic groups, indicating that the mutation is not limited to the Chinese population [33].

OCA Type 7

As the latest addition to the subtype of OCAs, OCA type 7 was identified in 2013 by Karen Grønskov and Thomas Rosenberg based on homozygosity mapping and gene sequencing of a consanguineous family with OCA symptoms on the Faroe Islands of Denmark [32]. The probands likewise as unrelated but affected individuals on the isle had homozygous not-sense mutation in C10orf11, a previously unknown gene that has been since shown to contribute to melanocyte differentiation. Production of OCA phenotype due to this factor mutation is thus termed OCA type 7[34].


There are two known types of ocular albinism (OA) without cutaneous involvement.

OA Type 1

"Mud-splattered" fundus due to areas of hypopigmentation interdigitating with normal pigmentation--seen in carrier females of OA blazon 1.

As well known as Nettleship-Falls ocular albinism, this disorder is inherited in an Ten-linked recessive manner and thus occurs only in boys. It is the well-nigh common class of ocular albinism representing 10% of all albinism and estimated prevalence of 1 in 50,000 to 150,000 live births [35] [36].
Mutations in GPR143 cistron at Xp22.3-22.2 are known to be causative [37]. The afflicted gene codes for intracellular GPCR (G-protein coupled receptor) that controls the melanosome transport in paint cells, disruption of which affects the number and size of the melanosomes. OA1 patients produce macromelanosomes seen on skin biopsy[7].
The clinical manifestation of OA1 depend on the ethnic groundwork of the individual, with those who are of darkly pigmented background existence less severely affected than those from calorie-free pigmentation groups [38] [39]. Albinism of the heart with OA tends to be severe with poor vision. Diagnostic methods include molecular analysis of OA1 gene (GPR143), family pedigree analysis, and exam of the carrier female parent. Due to lyonization of one X chromosome in each somatic cell, carrier females may showroom evidence of speckled albinism. In up to ninety% of carrier females, mud-splattered fundus is seen [xl] due to the patchy dissemination of amelanotic patches of RPE amidst melanotic patches. Other potential findings are iris transillumination in 75%, hypopigmented macules of the peel, and biopsy testify of macromelanosomes in those skin segments [41]. See OA2 for comparison. Of notation, OA1 has been associated with late-onset sensorineural deafness (OASD)[42].The syndrome is probable the outcome of a contiguous gene defect that includes OA1 gene. OASD shares similarities simply is simply etiologically distinct from Waardenburg Syndrome, which is characterized by patchy depigmentation of hair and skin, heterochromia irides, and congenital deafness [43].

OA Type two

Too known equally Aland Island eye disease or Forsius-Eriksson type ocular albinism, OA2 is a rare Ten-linked disorder with like clinical manifestations as OA1 with the additional protan color vision defect and defective night adaptation. In add-on to such differences, biopsy examination of skin samples from OA2 individuals revealed that OA2 is morphologically singled-out from OA1 [44]. Additionally, female person carriers of OA2 exercise not showroom characteristic fundus pattern seen in those of OA1 carriers. Based on molecular analysis, the defective gene that gives rise to this disorder is probable in Xp21.3-p21.two [45] for CACNA1F gene. The clinical findings, however, overlap with congenital stationary night blindness (CSNB2A). Due to similar features of OA2 and CSNB2A, Hawksworth et al raised the question of whether these ii entities are the aforementioned[46].

Mutations detected in genes associated with albinism

Table: Mutations detected in genes associated with albinism
Adjusted from Albinism for the decorated clinician, 2011 [seven].
Full name Abridgement Blazon Gene/poly peptide Locus Inheritance
Tyrosine negative OCA 1A OCA Tyrosinase 11q14-q21 AR
Xanthous variant OCA 1B OCA Tyrosinase 11q14-q21 AR
Minimal pigment OCA 1MP OCA Tyrosinase 11q14-q21 AR
Temperature sensitive OCA 1TS OCA Tyrosinase 11q14-q21 AR
OCA Type 2 OCA two OCA P gene / OCA2 15q11.2-q12 AR
Brownish albinism BOCA OCA P gene / OCA2 15q11.two-q12 15q11.2-q12
OCA Type three OCA iii / ROCA OCA Tyrosinase related poly peptide (TYRP1) 9p23 AR
OCA Type four OCA 4 OCA Membrane-associated transporter protein (MATP) = SLC45A2 5p13.3 AR
OCA Type 5 OCA v OCA Unknown 4q24 AR
OCA Blazon 6 OCA vi OCA SLC24A5 15q21.1 Ar
OCA Blazon seven OCA 7 OCA C10orf11 10q22 AR
Oculoalbinism 1 aka Nettleship-Falls ocular albinism OA 1 OA GPR143 Xp22.3 XR
Oculoalbinism two aka Forsius-Eriksson type ocular albinism OA ii OA CACNA1F Xp21.3-p21.two XR

Differential diagnoses

The syndromic forms of albinism are associated with defects in packing and trafficking of cellular proteins, thus distinct from oculocutaneous albinism divers by the defect of melanin product[47].

Hermansky-Pudlak Syndrome (HPS)

Ocular albinism is a component of Hermansky-Pudlak Syndrome, a rare autosomal recessive disorder that is farther characterized by haemorrhage tendency due to platelet storage deficiency, interstitial lung affliction, and granulomatous colitis (depending on the subtype)[48]. HPS is believed to be due to an aberration in the germination of intracellular vesicles such every bit melanosomes and the dense bodies of platelets almost commonly due to a mutation in HPS1 cistron on chromosome ten[7]. Considering HPS is seen well-nigh normally among those of Swiss or Puerto Rican descent at the prevalence of 1:1800[49], it should be suspected in patients with albinism with the relevant ethnic background plus the associated systemic symptoms.

Albinoidism

Albinidoism is an autosomal dominant mutation with incomplete penetrance that results in hypopigmentation. The afflicted patients have normal vision, retinal development, and no nystagmus. This phenotype may correspond the intermediate phenotype between wild type and true albinism with macular hypoplasia [seven].

Waardenburg Syndrome(WS)

WS is an autosomal ascendant disorder notable for patchy areas of depigmentation of the hair and skin in piebald-like distribution, heterochromia irides (pigment abnormality of the iris), and wide nasal root. The concurrence of congenital deafness that occurs in about 20% of the patients is a distinctive noncutaneous feature of the syndrome. An estimated 2 to 35% of all congenital deafness results from WS [50] . The mutation responsible for WS occurs in the transcription factors PAX3 and MITF [51].

Chediak-Higashi Syndrome (CHS)

Claret smear showing giant azurophilic granules in neutrophils, characteristic of Chediak-Higashi Syndrome.

This rare autosomal recessive disorder boasts less than 500 reported cases in the literature in the past 20 years [52] and is among the triad of rare diseases grouped together as "silvery hair syndromes" [53]. CHS presents with variable but oft intermediate form of hypopigmentation recurrent severe pyogenic infections that is ultimately lethal accompanied by progressive neurologic abnormalities, coagulation defects, and mucosal defects such as gingivitis, oral ulcerations, and periodontal diseases . The underlying defect of CHS is a mutation in the lysosomal trafficking regulator in the CHS1/LYST gene[52]. The resultant abnormal protein trafficking leads to dysfunctional fusion of vesicles and failure of transport of lysosomes to the appropriate intracellular site. The diagnosis should exist considered in a young patient—many patients do not live past early babyhood—presenting with OCA with the same systemic symptoms. Blood smear showing behemothic azurophilic granules in neutrophils, eosinophils, and other granulocytes is pathognomonic for CHS[54]. Bone marrow transplant is curative in some patients[55].

Griscelli Syndrome (GS)

Some other member of the silvery hair syndrome triad, GS is a rare autosomal-recessive disorder that results in hypopigmentation of peel and pilus (silver hair), neurologic deficit, with or without immunologic impairment or hematophagocytic syndrome. The severity of the diseases is determined by the involved gene-- MYO5A (GS blazon 1), RAB27A (GS type 2), and melanophilin (Mlph) (GS blazon iii). GS can be distinguished from CHS due to lack of giant intracellular granules that are seen in CHS.

Elejalde Syndrome (ES)

Non to exist confused with the acrocephalopolydactylous dysplasia, also known every bit Elejalde syndrome, this disease entity is synonymous with Neuroectodermal melanolysosomal disease [56]. Since first reported by Elejalde in 1977 [57], ES has been reported only x times in the literature, suggesting a startlingly depression prevalence of this affliction. The phenotype of ES includes silverish hair, tendency for easy tanning due to a defect in melanin processing, profound CNS dysfunction including hypotonia, hemi or quadriplegia, seizure, and developmental filibuster, and lack of immunologic disturbance. More than half of the patients in the 10 reported cases are presumed to have died in childhood [56]. Microscopic evaluation of the skin aids in differentiating this disease from GS and CHS. See tabular array below for key differences among the 3 Silvery Hair syndromes.

Differentiation of Syndromes with Silvery Hair

Table: Differentiation of Syndromes with Silvery Hair
(adopted from Cahali 2004)
Characteristics Chediak-Higashi Griscelli Elejalde
Age at Onset Infancy/early on childhood Infancy/early childhood Infancy/early on babyhood
Inheritance Autosomal recessive Autosomal recessive Autosomal recessive
Melanin in hair Pocket-size clumps, regular pattern Minor and large clumps, irregular pattern Small and big clumps, irregular pattern
Leukocytic granules Yes No No
Recurrent infections Yep Aye No
Neurologic harm Yes Yes Yeah
Allowed defects Diminished chemotaxis of neutrophils, decreased natural killer part, decreased antibiotic dependent cellular cytotoxicity Humoral and jail cell-mediated immunity disturbed None
Skin lite microscopy Large melanin granules in melanocytes and keratinocytes Hyperpigmented basal melanocytes with sparse pigmentation in adjacent keratinocytes Irregular distribution and irregular size of melanin granules in the basal layer
Skin electron microscopy Behemothic melanosomes in

melanocytes and keratinocytes

Accumulation of normal-size, mature melanosomes in melanocytes, few melanosomes in keratinocytes Melanocytes with different stages of melanosomes germination

Management

A medical exam to evaluate for the presence of a systemic syndrome is warranted in loftier-chance populations or when a history of bleeding, easy bruising, or previous bacterial infections is uncovered. Patients with albinism are at higher take chances for squamous cell and basal jail cell cancers in sun-exposed areas, and thus should be strongly encouraged to limit their lord's day exposure through avoiding outdoor occupations and through using sun-protective products such as advisable clothing, large-brim hats, sunglasses, and sunscreen agents.  An early eye examination is required to detect big refractive errors and to facilitate early on diagnosis and management of amblyopia. Patients with strabismus or nystagmus may do good from eye muscle surgery, so identification of such patients early may assistance optimize visual role.  Every bit with other heritable conditions, genetic testing and counseling support may offer invaluable support for families faced with this status.

Investigative Treatments

  • Nitisinone is an FDA-approved inhibitor of tyrosine degradation for hereditary tyrosinemia. Brooks and colleagues[58] hypothesized that the relative deficiency of tyrosinase in OCA blazon one may be ameliorated by increasing the concentration of tyrosine with nitisinone and thus improving pigmentation with OCA one. In mice studies, nitisinone indeed improved pigmentation in fur and irides, suggesting potential for benefit in humans affected by OCA 1.
  • A group past Martinez-Garcia et al [9] attempted to supplement L-DOPA, an intermediate metabolite of melanin synthesis pathway in mouse models. Various experiments suggested that L-DOPA supplementation may assistance overcome visual abnormalities associated with albinism[ix]. Stage 2 clinical trial (link to trial) is underway in the United states to study the effects of L-Dopa supplementation in human subjects[59].
  • A Japanese group suggested the apply of aminoglycosides that tin read through non-sense mutations for a potential treatment mensurate for common mutations found in albinism [60].

Prognosis

Lifespan, evolution, intelligence, and fertility in patients with OCA are not unlike from unaffected patients. With proper secondary prevention and supportive care for UV protection, the risk of skin cancer may be drastically reduced [iv],[61],[62],[63].

Additional Resources

  • Lee, KA (2012). FocalPoints Clinical Modules for Ophthalmologists: Pediatric Diagnoses You Don't Desire to Miss. American University of Ophthalmology. San Francisco, CA.
  • Porter D, Lipsky SN. Albinism. American Academy of Ophthalmology. EyeSmart® Eye health. https://world wide web.aao.org/eye-health/diseases/albinism-7. Accessed March 07, 2019.

References

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  2. ↑ 2.0 ii.1 Lund PM. Oculocutaneous albinism in southern Africa: population structure, wellness and genetic care. Ann Hum Biol. 2005 Mar-Apr;32(2):168-73. Review
  3. ↑ Traboulsi EI, Green WR. Duane'southward ophthalmology; Ch. 38 An Overview of Albinism and Its Visual System Manifestations. Lippincott Williams & Wilkins. 2006.
  4. ↑ 4.0 4.i 4.2 Hong ES, Zeeb H, Repacholi MH. Albinism in Africa as a public health issue. BMC Public Health. 2006 Aug 17;6:212
  5. ↑ Berger E, Chase R, Tzu J, Patel R, Sanchez M. Squamous-cell carcinoma in situ in a patient with oculocutaneous albinism. Dermatol Online J. 2011 October 15;17(x):22.
  6. ↑ Cruz-Inigo AE, Ladizinski B, Sethi A. Albinism in Africa: stigma, slaughter and awareness campaigns. Dermatol Clin. 2011 Jan;29(1):79-87.
  7. ↑ seven.0 7.ane 7.ii 7.3 7.4 7.5 7.vi 7.vii 7.8 vii.9 Levin AV, Stroh E. Albinism for the busy clinician. J AAPOS. 2011 Feb;15(i):59-66.
  8. ↑ Kumar A, Gottlob I, McLean RJ, Thomas S, Thomas MG, Proudlock FA. Clinical and oculomotor characteristics of albinism compared to FRMD7 associated infantile nystagmus. Invest Ophthalmol Vis Sci. 2011 Apr 8;52(5):2306-13.
  9. ↑ nine.0 9.1 9.two 9.3 Mártinez-García M, Montoliu L. Albinism in Europe. J Dermatol. 2013 May;40(five):319-24.
  10. ↑ Cooper DN, Ball EV, Krawczak One thousand. The human gene mutation database. Nucleic Acids Res. 1998 Jan one;26(ane):285-7.
  11. ↑ Hornyak TJ. The developmental biology of melanocytes and its application to understanding man built disorders of pigmentation. Adv Dermatol. 2006;22:201-18.
  12. ↑ Boissy RE, Nordlund JJ. Molecular basis of congenital hypopigmentary disorders in humans: a review. Paint Cell Res. 1997 Feb-April;10(1-2):12-24.
  13. ↑ RGiebel LB, Musarella MA, Spritz RA. A nonsense mutation in the tyrosinase gene of Afghan patients with tyrosinase negative (type IA) oculocutaneous albinism. J Med Genet. 1991 Jul;28(7):464-7.
  14. ↑ Grønskov M, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2;two:43.
  15. ↑ King RA, Wirtschafter JD, Olds DP, Brumbaugh J. Minimal pigment: a new type of oculocutaneous albinism. Clin Genet. 1986 Jan;29(1):42-50.
  16. ↑ Kono M, Kondo T, Ito S, Suzuki T, Wakamatsu K, Ito Due south, Tomita Y. Genotype analysis in a patient with oculocutaneous albinism one minimal pigment blazon. Br J Dermatol. 2012 Apr;166(four):896-8.
  17. ↑ Spritz RA, Oh J, Fukai K, Holmes SA, Ho L, Chitayat D, France TD, Musarella MA, Orlow SJ, Schnur RE, Weleber RG, Levin AV. Novel mutations of the tyrosinase (TYR) gene in blazon I oculocutaneous albinism (OCA1). Hum Mutat. 1997;10(ii):171-4.
  18. ↑ Fridman C, Hosomi North, Varela MC, Souza AH, Fukai 1000, Koiffmann CP. Angelman syndrome associated with oculocutaneous albinism due to an intragenic deletion of the P gene.Am J Med Genet A. 2003 Jun 1;119A(2):180-iii.
  19. ↑ Nicholls RD, Bailin T, Mascari MJ, Butler MG, Spritz RA. Hypopigmentation in the Prader-Willi syndrome correlates with P gene deletion but not with haplotype of the hemizygous P allele. Am J Hum Genet. 1996;59:A39.
  20. ↑ King RA, Creel D, Cervenka J, Okoro AN, Witkop CJ. Albinism in Nigeria with depiction of new recessive oculocutaneous blazon. Clin Genet. 1980 April;17(4):259-lxx.
  21. ↑ 21.0 21.1 Rex RA, Lewis RA, Townsend D, Zelickson A, Olds DP, Brumbaugh J. Brown oculocutaneous albinism. Clinical, ophthalmological, and biochemical characterization. Ophthalmology. 1985 November;92(eleven):1496-505.
  22. ↑ Rex RA, Rich SS. Segregation analysis of brown oculocutaneous albinism. Clin Genet. 1986;29:496–501.
  23. ↑ Manga P, Kromberg J, Turner A, Jenkins T, Ramsay Chiliad. In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified. Am J Hum Genet. 2001;68:782–7.
  24. ↑ Zhang KH, Li Z, Lei J, Pang T, Xu B, Jiang WY, Li HY. Oculocutaneous albinism blazon 3 (OCA3): assay of 2 novel mutations in TYRP1 cistron in two Chinese patients. Jail cell Biochem Biophys. 2011 Dec;61(3):523-nine.
  25. ↑ Rooryck C, Morice-Picard F, Elçioglu NH, Lacombe D, Taieb A, Arveiler B. Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes and practical aspects. Pigment Cell Melanoma Res. 2008 Oct;21(5):583-seven.
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  30. ↑ Kausar T, Bhatti MA, Ali M, Shaikh RS, Ahmed ZM. OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q24. Clin Genet. 2013 Jul;84(1):91-3.
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  32. ↑ 32.0 32.1 Grønskov Thou, Dooley CM, Østergaard Due east, Kelsh RN, Hansen L, Levesque MP, Vilhelmsen K, Møllgård M, Stemple DL, Rosenberg T. Mutations in c10orf11, a melanocyte-differentiation cistron, crusade autosomal-recessive albinism.Am J Hum Genet. 2013 Mar 7;92(3):415-21
  33. ↑ Morice-Picard F, Lasseaux Due east, François S, Simon D, Rooryck C, Bieth Due east, Colin E, Bonneau D, Journel H, Walraedt S, Leroy BP, Meire F, Lacombe D, Arveiler B. SLC24A5 Mutations Are Associated with Non-Syndromic Oculocutaneous Albinism. J Invest Dermatol. 2013 Aug 28.
  34. ↑ Montoliu 50, Grønskov 1000, Wei AH, Martínez-García Grand, Fernández A, Arveiler B, Morice-Picard F, Riazuddin Due south, Suzuki T, Ahmed ZM, Rosenberg T, Li West. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res. 2013 Sep 21.
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  42. ↑ Winship IM, Babaya M, Ramesar RS. X-linked ocular albinism and sensorineural deafness: linkage to Xp22.3. Genomics. 1993 Nov;xviii(2):444-5.
  43. ↑ Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg syndrome. Int J Dermatol. 1999;38(nine):656.
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  45. ↑ Pillers DA, Towbin JA, Chamberlain JS, Wu D, Ranier J, Powell BR, McCabe ER. Deletion mapping of Aland Isle eye disease to Xp21 between DXS67 (B24) and Duchenne muscular dystrophy. Am J Hum Genet. 1990 Nov;47(5):795-801
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  47. ↑ Scheinfeld NS. Syndromic albinism: a review of genetics and phenotypes. Dermatol Online J. 2003 December;nine(5):v.fckLR Seward SL Jr, Gahl WA. Hermansky-Pudlak syndrome: health care throughout life. Pediatrics. 2013 Jul;132(1):153-sixty.fckLR
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  53. ↑ Reddy RR, Babu BM, Venkateshwaramma B, Hymavathi Ch. Silvery hair syndrome in two cousins: Chediak-Higashi syndrome vs Griscelli syndrome, with rare associations. Int J Trichology. 2011 Jul;3(2):107-11.
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  57. ↑ Elejalde B, Valencia A, Gilbert East, Marin Thou, Molina J, Holguin J. 1977. Neuro-ectodermal melanolysosomal disease: An autosomal recessive pigment mutation in man. Am J Hum Genet 29: 39A.
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  59. ↑ Lavado A, Jeffery G, Tovar 5, de la Villa P, Montoliu L. Ectopic expression of tyrosine hydroxylase in the pigmented epithelium rescues the retinal abnormalities and visual function mutual in albinos in the absence of melanin. J Neurochem. 2006 Feb;96(4):1201-eleven.
  60. ↑ K. Fukai, H. Kunimoto, K. Nakajima, T. Suzuki, G. Ishii. In vitro assay of read-through effect of aminoglycosides to tyrosinase R278X nonsense mutation in melan-c cells. The 24th Annual Coming together of the Japanese Society for Pigment Jail cell Research (JSPCR-2012) xix OCT 2012
  61. ↑ Ramalingam VS, Sinnakirouchenan R, Thappa DM: Malignant transformation of actinic keratoses to squamous cell carcinoma in an albino. Indian J Dermatol 2009, 54:46-48.
  62. ↑ Okoro AN: Albinism in Nigeria. A clinical and social report. Br J Dermatol 1975, 92:485-492.
  63. ↑ Chalya PL, Gilyoma JM, Kanumba ES, Mawala B, Masalu North, Kahima JK, Rambau P: Dermatological malignancies at a University Educational activity Hospital in north-western Tanzania: a retrospective review of 154 cases. Tanzania Journal of Health Research 2021, xiv(1):1-7.

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