OCA1 in different ethnic groups of India is primarily due to founder mutations in the tyrosinase gene
OCA1 in different ethnic groups of India is primarily due to founder mutations in the tyrosinase gene
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DOI：
10.1111/j.1469-1809.2006.00247.x
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发表时间：
2006-09-01
影响因子：
1.9
通讯作者：
Ray, K.
中科院分区：
文献类型：
--
作者：
Chaki, M.;Sengupta, M.;Ray, K.
眼皮肤白化病 (OCA) 是一组异质性常染色体隐性遗传疾病，其特征是眼睛、皮肤和头发中黑色素含量异常低，并与常见的眼睛发育异常相关。酪氨酸酶基因 (TYR) 缺陷会导致一种常见类型的 OCA，称为 1 型眼皮肤白化病 (OCA1)。 OCA 的分子基础已在不同人群中进行了广泛研究，但有关印度患者的信息很少。我们的调查涵盖印度 13 个民族，其中一些民族代表超过 2000 万人，结果显示，在 25 个 OCA 家庭中，有 12 个受到 OCA1 的影响，这些病例主要是由于 TYR 的创始人突变所致。我们在 TYR 中检测到 9 个突变和 8 个 SNP，其中 6 个突变（5 个点突变和 1 个总缺失）是新的。与大多数描述复合杂合子的报告相反，12 个谱系中有 10 个存在纯合子，这突显了印度这些族群之间缺乏混杂。单倍型分析表明，一些创始人染色体导致了大多数患者的疾病。直接检测特定种族中普遍存在的突变可用于携带者检测和遗传咨询。
Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders characterized by an abnormally low amount of melanin in the eyes, skin and hair, and associated with common developmental abnormalities of the eye. Defects in the tyrosinase gene (TYR) cause a common type of OCA, known as oculocutaneous albinism type 1 (OCA1). The molecular basis of OCA has been studied extensively in different population groups, but very little information is available on Indian patients. Our investigation covering thirteen ethnic groups of India, some representing > 20 million people, revealed that among 25 OCA families 12 were affected with OCA1, and that these cases were primarily due to founder mutations in TYR. We detected nine mutations and eight SNPs in TYR, of which six mutations (five point mutations & one gross deletion) were novel. In contrast to most reports describing compound heterozygotes, the presence of homozygotes in 10 out of the 12 pedigrees underscores the lack of intermixing between these ethnic groups in India. Haplotype analysis suggested a few founder chromosomes causing the disease in the majority of the patients. Direct detection of the mutations prevalent in specific ethnic groups could be used for carrier detection and genetic counselling.