Increasing the complexity: new genes and new types of albinism.

Albinism is a rare genetic condition globally characterized by a number of specific deficits in the visual system, resulting in poor vision, in association with a variable hypopigmentation phenotype. This lack or reduction in pigment might affect the eyes, skin, and hair (oculocutaneous albinism, OCA), or only the eyes (ocular albinism, OA). In addition, there are several syndromic forms of albinism (e.g. Hermansky-Pudlak and Chediak-Higashi syndromes, HPS and CHS, respectively) in which the described hypopigmented and visual phenotypes coexist with more severe pathological alterations. Recently, a locus has been mapped to the 4q24 human chromosomal region and thus represents an additional genetic cause of OCA, termed OCA5, while the gene is eventually identified. In addition, two new genes have been identified as causing OCA when mutated: SLC24A5 and C10orf11, and hence designated as OCA6 and OCA7, respectively. This consensus review, involving all laboratories that have reported these new genes, aims to update and agree upon the current gene nomenclature and types of albinism, while providing additional insights from the function of these new genes in pigment cells.

TYPES OF ALBINISM IN THE BLACK SOUTHERN AFRICA POPULATION.

BACKGROUND: Oculocutaneous albinism (OCA) is the most common inherited disorder in Southern African blacks and several types have been described. Molecular techniques, where available, can be used to confirm a clinical diagnosis and the type of OCA, if necessary, and for prenatal diagnosis. OBJECTIVES: To investigate and classify the different types of albinism commonly found and to determine the clinical implications for each type. DESIGN: A descriptive survey. SETTING: Gauteng province, South Africa, and Lesotho. SUBJECTS: Three groups of subjects with OCA (96 from a genetics clinic, 62 from a dermatology clinic, and 31 from community surveys) from the black African population participated. MAIN OUTCOME MEASURES: Subjects underwent clinical and/or dermatological examinations and were then classified according to type of OCA. RESULTS: Four forms of OCA were identified: most (82%) subjects had OCA2 (a tyrosinase- positive type) with three sub-types: those without large freckles (ephelides) on exposed areas (named OCA 2a in this study), those with such freckles (named OCA 2b), and those with brown albinism (BOCA); the remainder had red/rufous albinism, ROCA (OCA 3). The four forms could be distinguished from each other clinically without using molecular genetic testing. CONCLUSION: The most common types of albinism found in the black population of Southern Africa are OCA2 and OCA3. Given the high prevalence of the disorder, together with the high risk of skin cancer, and the recent persecution of affected individuals in certain East African countries, these findings and their clinical implications have significance in terms of both education and awareness for health professionals and lay people caring for those with albinism.

Albinism: classification, clinical characteristics, and recent findings.

PURPOSE: To describe the clinical characteristics and recent findings in the heterogeneous group of inherited disorders of melanin biosynthesis grouped as "albinism." METHODS: The current classification of albinism, and the cutaneous, ocular, and central nervous system characteristics are presented. Recent clinical findings are summarized. RESULTS: Albinism is now classified based on genes known to be responsible for albinism. Foveal hypoplasia is invariably present and individuals with albinism often have delayed visual development, reduced vision, nystagmus, a positive angle kappa, strabismus, iris transillumination, and absent or reduced melanin pigment in the fundi. A visual-evoked potential can document the excessive retinostriate decussation seen in albinism. Grating acuity can be used to document delayed visual development in preverbal children. Glasses are often needed to improve visual acuity and binocular alignment. CONCLUSIONS: Albinism is caused by several different genes. Heterogeneity in clinical phenotype indicates that expressivity is variable.

Pigmentary disorders in China.

Because variations in the degrees of pigmentation occur in various regions of the body, there are different pigmentary diseases in various ethnic groups. We usually divide the disorders of melanin pigmentation into two types: hypermelanosis and hypomelanosis. These disorders may be due to genetic and environmental factors. Pigmentary disorders are more visible on the Chinese skin and are of great cosmetic concern to patients. In this article we introduce characteristic pigmentary disorders in China.

Mutation analysis of the tyrosinase gene in oculocutaneous albinism.

Type I oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by the reduction or the absence of tyrosinase (TYR) activity in melanocytes of the skin, hair and eyes. Here we report an analysis of 45 patients with OCA. We found five novel mutations in the tyrosinase gene involved in the pathogenesis of oculocutaneous albinism type IA or type IB (OCA-1A/B) in five unrelated patients. Three mutations are missense mutations (G109R, P205T and H256Y) and two are nucleotide deletions (336-337delCA and 678-680delAGG). One patient is homozygous for the previously known V275F mutation but has an extremely mild OCA phenotype and has no eye features typical of OCA. In several patients we discovered only one or even no mutation in the coding sequence of the TYR gene. Thus, this disease may also result from mutations in non coding regions of the gene or in another gene involved in the biosynthesis of melanin. Hum Mutat 17:352, 2001.

Albinism: an update.

Albinism connotes a large group of genetic disorders that are characterized by diminished ocular and oftentimes cutaneous pigmentation. These disorders are generally subclassified as oculocutaneous albinism (OCA) or ocular albinism (OA) based on the extent of their effects on the pigmentation of the skin and hair. Sometimes, different mutations in the same gene can cause OCA or OA.

The molecular genetics of albinism and piebaldism.

BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal-recessive genetic disorder defined by hypomelanosis in the eyes, hair, and skin. Piebaldism is an autosomal-dominant congenital leukoderma associated with a white forelock. The molecular pathogeneses of these congenital pigmentary disorders have been clarified in recent years and are briefly reviewed here. OBSERVATIONS: The pathologic gene mutations causing OCA and piebaldism are as follows. When a mutated tyrosinase gene produces inactive, less active, or temperature-sensitive tyrosinase, its phenotype is tyrosinase-negative (type I-A), yellow-mutant (type I-B), or temperature-sensitive (type I-TS) OCA, respectively. Mutation of the P gene encoding the tyrosine-transporting membrane protein probably occurs in tyrosinase-positive OCA (type II). A heterozygous mutation of the c-kit gene encoding mast cell-stem cell growth factor receptor induces piebaldism. CONCLUSION: The molecular bases of several types of OCA and piebaldism have been elucidated by gene technology, and other gene mutations causing OCA or many other pigmentary disorders will be clarified in the near future.

Variable expression of albinism within a single kindred.

We studied the albinotic characteristics in 13 members of a white family (age range, 2 to 73 years), which were graded according to severity and were correlated with visual acuity. Clinical, electrophysiologic, and biochemical characteristics of this family do not fit any known category of human albinism. The degree of heterogeneity in expression of albinotic features was unexpected. The correlation between visual acuity and nystagmus was particularly strong. The brown-haired propositus had severe skin involvement, iris transillumination, fundus hypopigmentation, and foveal hypoplasia. He had no manifest nystagmus, however, and his visual acuity was nearly normal. These observations suggest that nystagmus imposes a visual deficit beyond that related to foveal hypoplasia alone.

Autosomal albinism affects immunocompetence in the chicken.

Immune responsiveness of three neonatal and juvenile phenotypes, determined by the albinotic C locus, was evaluated. The phenotypes included normally pigmented (C+/-), recessive white (c/ca), and completely amelanotic albinos (ca/ca). No differences in: (1) primary agglutinin levels directed against sheep red blood cells (SRBC) or Brucella abortus (BA), or (2) cell-mediated immunity, as estimated by in vivo mitogen stimulation, were associated with the albino phenotype. The significant suppression of secondary SRBC or BA agglutinins observed in albino chicks was limited and of questionable biological significance. Acquisition of passively transferred maternal BA agglutinins was significantly impaired in albino progeny irrespective of dam genotype. No differences in agglutinin levels were associated with dam genotype. In addition, uptake of yolk sac contents was retarded significantly in albino chicks at hatch. These data suggest that an impaired ability to absorb maternal antibody and not the capacity to mount an active immune response contributes to neonatal mortality in albino chicks.

Albinism.

Genetic abnormalities of the melanin pigment system in which the synthesis of melanin is reduced or absent are called albinism. The reduction in melanin synthesis can involve the skin, hair follicle, and eye, resulting in oculocutaneous albinism, or can be localized primarily to the eye, resulting in ocular albinism. Approximately 1 in 17,000 individuals in the United States has oculocutaneous albinism, and more than 1 per cent of the population are heterozygous for a gene producing albinism.

Development of the subfornical organ and area postrema of the male albino mouse. Karyometric effect of neonatal and prepuberal castration.

We have studied the karyometric development of the nuclei of the ependymal cells and neurons of the subfornical organ and the area postrema in the male albino mouse from the 5th to the 190th postnatal day. We have found similar patterns of development in both although the area postrema showed more significant postnatal oscillations than those of the subfornical organ, suggesting a more intimate chronological relationship to gonadal development. We have furthermore analyzed the development in two experimental groups: in the one animals were castrated at birth, in the other, castration was made on the 20th postnatal day. We have found that neonatal castration produced a significant decrease of nuclear sizes; this was more evident in the subfornical organ than in the area postrema in earlier stages of development while the response was similar in both at peripuberal ages. The response to prepuberal castration was similar in both organs.

Albinism, or the NOACH syndrome (the book of Enoch c.v. 1-20).

UNLABELLED: After a 4-year multidisciplinary study of albinism our findings will be presented here. Over a hundred albinos were examined, together with their heterozygote family members. Given this substantial patient and subject sample we were provided with the opportunity to: evaluate the results of standard diagnostic procedures, for example pedigree analysis, ocular and clinical examination; determine the diagnostic value of biochemical, and ultrastructural tests; and develop a new and viable albino diagnostic protocol, particularly for electrophysiological examination. In the conclusions the following subjects are in order: DIAGNOSIS: Our most important finding up till now is that normally pigmented people who do not look like albinos can in fact be albinos. DIFFERENTIAL DIAGNOSIS: It appears that patients with autosomal recessive albinism can be normally pigmented, and patients with X-linked albinism can be severely hypopigmented. We therefore propose to abandon the terms oculo-cutaneous albinism (OCA), and X-linked ocular albinism (XOA), and use the terms autosomal recessive albinism, and X-linked albinism instead. X-linked albinism Forsius-Eriksson type (XOAF): We assume that XOAF does not represent a true form of albinism. CLASSIFICATION: Our results indicate that the phenotypical albino classification, which was a base for Witkop et al. (1978) to also obtain a genetical classification, supported by the hairbulb test, has not proved to be useful for the classification of tyrosinase negative (TNOCA), tyrosinase positive oculocutaneous albinism (TPOCA), and autosomal recessive ocular albinism (AROA) as genetically distinct forms. Prevalence: Our prevalence estimate for all forms of albinism is at least 1:15,000, about 10% of the albinos have X-linked albinism. DEFINITION: We want to modify the albino definition as a hereditary and congenital inborn error of metabolism related to the pigment cell, and resulting in a systemic disorder that is characterized by anomalies of eyes, and hypopigmentation in most cases or absence of pigment in skin, hair, and eyes, and of which the neuro-anatomical consequences are the most characteristic.

Albinism.

Albinism is the term applied to a heterogeneous group of genetically determined disorders characterized by hypopigmentation and affecting the eyes. After describing the clinical features of albinism in general, the authors discuss the various forms of oculocutaneous albinism, ocular albinism, and albinoidism that are of interest to the ophthalmologist. Emphasis is placed on the ocular features of each form. The visual pathway abnormalities and the clinical management of albinism are discussed.