Department of Genetics, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, India.
Vivekananda Mission Ashram Netra Niramay Niketan, Purba Midnapore, Haldia, West Bengal, India.
Mol Biol Rep. 2024 Jul 16;51(1):818. doi: 10.1007/s11033-024-09777-y.
Oculocutaneous albinism (OCA) is a congenital heterogeneous group of autosomal recessive disorders characterized by the absence or loss of melanin in the skin, eyes and hair of the affected individuals. Based on the mutated gene, OCA has been classified into eight sub-types (OCA1-8) with overlapping clinical phenotypes. Mutations in the TYR gene cause OCA1, the most prevalent OCA worldwide including India. Mutations in OCA2 and SLC45A2, both of which regulate melanosomal pH that is critical to TYR activity, cause OCA2 and OCA4 respectively, the other common OCA subtypes in India.
In the present study, we have included 54 OCA-affected cases from 41 unrelated families representing 16 different marriage/ethnic groups from 17 districts of West Bengal, India. We pursued a PCR-sequencing based approach followed by bioinformatic analysis to identify mutations in TYR, OCA2 and SLC45A2 genes.
Mutations were detected in 27 of the 54 (50%) OCA patients from 18 unrelated families, representing 9 different marriage/ethnic groups from 11 districts of West Bengal. Three TYR variants: NM_000372.4: c.391 A > G, NP_000363.1: p. Lys131Glu; NM_000372.4: c.1037G > T; NP_000363.1: p. Gly346Val, NM_000372.4: c.715 C > T; NP_000363.1:p.Arg239Trp was identified for the first time in Eastern Indian OCA cases. A novel nonsense variant: NM_016180.5: c.389 T > A, NP_057264.4: p. Leu130* and a novel synonymous variation NM_016180.5: c.1092 A > G; NP_057264.4: p.364E = were identified in SLC45A2. Additionally, NM_016180.5: c.904A > T; NP_057264.4: p. Thre302Ser was identified for the first time in any Eastern Indian OCA case. We identified 2 previously reported mutations in OCA2. In concordance with previous reports, NM_000372.4: c.832C > T, NP_000363.1: p. (Arg278*) was the commonest TYR mutation.
The results of our study enrich the mutational spectrum of the known OCA causing genes in Eastern India, which would facilitate accurate diagnosis, familial screening, carrier detection and containment of the disease load.
眼皮肤白化病（Oculocutaneous albinism，OCA）是一组常染色体隐性遗传的先天性异质性疾病，其特征是受影响个体的皮肤、眼睛和头发中黑色素的缺失或丧失。根据突变基因，OCA 已分为八个亚型（OCA1-8），具有重叠的临床表型。TYR 基因的突变导致 OCA1，这是全世界包括印度最常见的 OCA 类型。OCA2 和 SLC45A2 基因突变分别导致 OCA2 和 OCA4，这是印度其他常见的 OCA 亚型，这两个基因都调节黑色素体的 pH 值，这对 TYR 活性至关重要。
在本研究中，我们纳入了来自印度西孟加拉邦 17 个区的 41 个无关家庭的 54 名 OCA 患者，代表了 16 个不同的婚姻/族裔群体。我们采用了基于 PCR 测序的方法，并进行了生物信息学分析，以鉴定 TYR、OCA2 和 SLC45A2 基因的突变。
在来自西孟加拉邦 11 个区的 9 个不同婚姻/族裔群体的 18 个无关家庭的 54 名 OCA 患者中的 27 名（50%）检测到了突变。三种 TYR 变异：NM_000372.4：c.391 A>G，NP_000363.1：p.Lys131Glu；NM_000372.4：c.1037G>T；NP_000363.1：p.Gly346Val，NM_000372.4：c.715 C>T；NP_000363.1：p.Arg239Trp 首次在印度东部的 OCA 病例中被发现。一种新的无义变异：NM_016180.5：c.389 T>A，NP_057264.4：p.Leu130和一种新的同义变异 NM_016180.5：c.1092 A>G；NP_057264.4：p.364E=在 SLC45A2 中被发现。此外，NM_016180.5：c.904 A>T；NP_057264.4：p.Thr302Ser 首次在任何印度东部的 OCA 病例中被发现。我们在 OCA2 中发现了两种先前报道的突变。与先前的报道一致，NM_000372.4：c.832C>T，NP_000363.1：p.（Arg278）是最常见的 TYR 突变。
我们的研究结果丰富了印度东部已知 OCA 致病基因的突变谱，这将有助于准确诊断、家族筛查、携带者检测和疾病负荷的控制。
