Copyright © 2001 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 68, Issue 3, 782-787, 1 March 2001
doi:10.1086/318800
Report
In Southern Africa, Brown Oculocutaneous Albinism (BOCA) Maps to the OCA2 Locus on Chromosome 15q: P-Gene Mutations Identified
Prashiela Mangaa, Jennifer G.R. Kromberga, Angela Turnera, Trefor Jenkinsa and Michele Ramsaya, 
Address for correspondence and reprints: Dr. Michele Ramsay, Department of Human Genetics, School of Pathology, the South African Institute for Medical Research and University of the Witwatersrand, PO Box 1038, Johannesburg, 2000, South AfricaAbstract
In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; θ=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype.
Article Information
PubMed
Related Articles
- Rufous Oculocutaneous Albinism in Southern African Blacks Is...Rufous Oculocutaneous Albinism in Southern African Blacks Is Caused by Mutations in the TYRP1 Gene
The American Journal of Human Genetics, Volume 61, Issue 5, 1 November 1997, Pages 1095-1101
P. Manga, J.G.R. Kromberg, N.F. Box, R.A. Sturm, T. Jenkins and M. Ramsay
AbstractSummary: Oculocutaneous albinism (OCA) is the most common autosomal recessive disorder among southern African Blacks. There are three forms that account for almost all OCA types in this region. Tyrosinase-positive OCA (OCA2), which is the most common, affects ∼1/3,900 newborns and has a carrier frequency of ∼1/33. It is caused by mutations in the P gene on chromosome 15. Brown OCA (BOCA) and rufous OCA (ROCA) account for the majority of the remaining phenotypes. The prevalence of BOCA is unknown, but for ROCA it is ∼1/8,500. Linkage analysis performed on nine ROCA families showed that ROCA was linked to an intragenic marker at the TYRP1 locus (maximum LOD score = 3.80 at θ=.00). Mutation analysis of 19 unrelated ROCA individuals revealed a nonsense mutation at codon 166 (S166X) in 17 (45%) of 38 ROCA chromosomes, and a second mutation (368delA) was found in an additional 19 (50%) of 38 chromosomes; mutations were not identified in the remaining 2 ROCA chromosomes. In one family, two siblings with a phenotypically unclassified form of albinism were found to be compound heterozygotes for mutations (S166X/368delA) at the TYRP1 locus and were heterozygous for a common 2.7-kb deletion in the P gene. These findings have highlighted the influence of genetic background on phenotype, in which the genotype at one locus can be influenced by the genotype at a second locus, leading to a modified phenotype. ROCA, which in southern African Blacks is caused by mutations in the TYRP1 gene, therefore should be referred to as “OCA3,” since this is the third locus that has been shown to cause an OCA phenotype in humans.
Abstract | | - Oculocutaneous Albinism Type 4 Is One of the Most Common Typ...Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in Japan
The American Journal of Human Genetics, Volume 74, Issue 3, 1 March 2004, Pages 466-471
Katsuhiko Inagaki, Tamio Suzuki, Hiroshi Shimizu, Norihisa Ishii, Yoshinori Umezawa, Joji Tada, Noriaki Kikuchi, Minoru Takata, Kenji Takamori, Mari Kishibe, Michi Tanaka, Yoshinori Miyamura, Shiro Ito and Yasushi Tomita
AbstractOculocutaneous 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.
Abstract | | - Mutations in the Human Orthologue of the Mouse underwhite Ge...Mutations in the Human Orthologue of the Mouse underwhite Gene (uw) Underlie a New Form of Oculocutaneous Albinism, OCA4
The American Journal of Human Genetics, Volume 69, Issue 5, 1 November 2001, Pages 981-988
J.M. Newton, Orit Cohen-Barak, Nobuko Hagiwara, John M. Gardner, Muriel T. Davisson, Richard A. King and Murray H. Brilliant
AbstractOculocutaneous albinism (OCA) affects ∼1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for ∼40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for ∼50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as “rufous/red albinism,” is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed “OCA4.” The encoded protein, MATP (for “membrane-associated transporter protein”) is predicted to span the membrane 12 times and likely functions as a transporter.
Abstract | | - …more
