Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in Japan

Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
The American Journal of Human Genetics (Impact Factor: 10.93). 03/2004; 74(3):466-71. DOI: 10.1086/382195
Source: PubMed


Oculocutaneous albinism (OCA) is a complex genetic disease with great clinical heterogeneity. Four different types of OCA have been reported to date (OCA1, OCA2, OCA3, and OCA4). MATP was recently reported in a single Turkish OCA patient as the fourth pathological gene, but no other patients with OCA4 have been reported. Here, we report the mutational profile of OCA4, determined by genetic analysis of the MATP gene in a large Japanese population with OCA. Of 75 unrelated patients that were screened, 18 individuals (24%) were identified as having OCA4; they harbored seven novel mutations, including four missense mutations (P58S, D157N, G188V, and V507L) and three frameshift mutations (S90CGGCCA-->GC, V144insAAGT, and V469delG), showing that MATP is the most frequent locus for tyrosinase-positive OCA in Japanese patients. We discuss the functional melanogenic activity of each mutant allele, judging from the relationship between the phenotypes and genotypes of the patients. This is the first report on a large group of patients with OCA4.

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    • "OCA3, or rufous OCA (ROCA), is virtually unseen in Caucasians but affects approximately one in 8,500 individuals from southern Africa or 3% of cases worldwide [14]. OCA-4 is also rare among Caucasians as well as Africans, but worldwide it accounts for 17% of cases and in Japan it is diagnosed in one of four persons affected with OCA [14, 20]. "
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    ABSTRACT: Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by either complete lack of or a reduction of melanin biosynthesis in the melanocytes. The OCA1A is the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3, and OCA4 show some pigment accumulation over time. Mutations in TYR, OCA2, TYRP1, and SLC45A2 are mainly responsible for causing oculocutaneous albinism. Recently, two new genes SLC24A5 and C10orf11 are identified that are responsible to cause OCA6 and OCA7, respectively. Also a locus has been mapped to the human chromosome 4q24 region which is responsible for genetic cause of OCA5. In this paper, we summarized the clinical and molecular features of OCA genes. Further, we reviewed the screening of pathological mutations of OCA genes and its molecular mechanism of the protein upon mutation by in silico approach. We also reviewed TYR (T373K, N371Y, M370T, and P313R), OCA2 (R305W), TYRP1 (R326H and R356Q) mutations and their structural consequences at molecular level. It is observed that the pathological genetic mutations and their structural and functional significance of OCA genes will aid in development of personalized medicine for albinism patients.
    BioMed Research International 06/2014; 2014(1):905472. DOI:10.1155/2014/905472 · 1.58 Impact Factor
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    • "The virtual absence of pigmentation is normally only observed with some OCA1 (i.e., OCA1A; King et al., 2003) and OCA4 individuals. The phenotype of OCA4 is very variable, from just similar to OCA1A to near normal, among Japanese patients (Inagaki et al., 2004; Suzuki and Tomita, 2008). The other OCA types (OCA2, OCA3, "
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    ABSTRACT: 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 of 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. This article is protected by copyright. All rights reserved.
    Pigment Cell & Melanoma Research 09/2013; 27(1). DOI:10.1111/pcmr.12167 · 4.62 Impact Factor
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    • "Oculocutaneous albinism type 4 (OCA4, OMIM# 606574) is a rare form of OCA except in Japan. Affected individuals have varying degrees of ocular and cutaneous hypopigmentation with visual acuity ranging from 20/30 to 20/400 [13,14]. OCA4 is caused by autosomal recessive mutations in the solute carrier 45, member 2 gene (SLC45A2) on 5p13.2 [15]. "
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    ABSTRACT: Background Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations in SLC45A2. Methods We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. Results The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. Conclusions This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.
    BMC Medical Genetics 11/2012; 13(1):111. DOI:10.1186/1471-2350-13-111 · 2.08 Impact Factor
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