背景:眼皮肤白化病(OCA)是一种先天性异质性的常染色体隐性遗传疾病,其特征是皮肤中黑色素的缺失或缺失,受影响个体的眼睛和头发。基于变异的基因,OCA已被分为八种亚型(OCA1-8),具有重叠的临床表型。TYR基因突变导致OCA1,包括印度在内的全球最普遍的OCA。OCA2和SLC45A2中的突变,两者都调节对TYR活性至关重要的黑色素体pH,分别导致OCA2和OCA4,印度其他常见的OCA亚型。
方法:在本研究中,我们纳入了54例受OCA影响的病例,来自西孟加拉邦17个地区的41个不相关家庭,代表16个不同的婚姻/种族群体,印度。我们采用基于PCR测序的方法,然后进行生物信息学分析以鉴定TYR中的突变,OCA2和SLC45A2基因。
结果:在来自18个无关家庭的54例OCA患者中的27例(50%)中检测到突变,代表来自西孟加拉邦11个地区的9个不同的婚姻/种族群体。三种TYR变体:NM_000372.4:c.391A>G,NP_000363.1:p.Lys131Glu;NM_000372.4:c.1037G>T;NP_000363.1:p.Gly346Val,NM_000372.4:c.715C>T;NP_000363.1:p。在印度东部OCA病例中首次发现Arg239Trp。一种新颖的无义变体:NM_016180.5:c.389T>A,NP_057264.4:p.Leu130*和一个新的同义变异NM_016180.5:c.1092A>G;NP_057264.4:p.364E=在SLC45A2中鉴定。此外,NM_016180.5:c.904A>T;NP_057264.4:p.Thre302Ser在任何印度东部OCA病例中首次被发现。我们在OCA2中鉴定了2个先前报道的突变。根据以前的报告,NM_000372.4:c.832C>T,NP_000363.1:p.(Arg278*)是最常见的TYR突变。
结论:我们的研究结果丰富了印度东部已知的OCA致病基因的突变谱,这将有助于准确诊断,家族筛查,载体检测和遏制疾病负荷。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.