Retrospective analysis in oculocutaneous albinism patients for the 2.7 kb deletion in the OCA2 gene revealed a co-segregation of the controversial variant, p.R305W.
Retrospective analysis in oculocutaneous albinism patients for the 2.7 kb deletion in the OCA2 gene revealed a co-segregation of the controversial variant, p.R305W.
复制标题
DOI：
10.1186/s13578-017-0149-3
复制
发表时间：
2017
影响因子：
7.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Gao J;D'Souza L;Wetherby K;Antolik C;Reeves M;Adams DR;Tumminia S;Wang X
眼皮肤白化病（OCA）是一种常染色体隐性遗传病。很大一部分 OCA 患者在 TYR 或 OCA2 基因中发现单一致病性变异。 TYR 和 OCA2 基因的诊断测序通常用于 OCA 亚型的分子诊断。为了研究涉及单个或多个外显子的基因组异常可能解释部分潜在缺失致病性变异（第二个）的可能性，我们通过长程 PCR 回顾性分析了 TYR 基因，并分析了目标基因中具有单个致病性变异的 OCA 患者中跨外显子 7 的 OCA2 基因中的目标 2.7 kb 缺失。在分析的 108 名患者中，我们发现一名患者的 2.7 kb OCA2 基因缺失是杂合的，并且该患者的一种致病性变异和一种可能致病性变异呈阳性 [c.1103C>T (p.Ala368Val) + c.913C>T (p.R305W)]。对母体 DNA 和另外两个 2.7 kb 缺失纯合的 OCA DNA 的进一步分析表明，表型正常的母亲是 2.7 kb 缺失的杂合子和 p.R305W 的纯合子。先前报道的两名具有 2.7 kb 缺失纯合子的患者也是 p.R305W 纯合子。在已报道的致病变异中，p.R305W 的致病性已在文献中进行了深入讨论。我们的结果表明 p.R305W 不太可能是致病变异。还表明 p.R305W 与 OCA2 基因中 2.7 kb 缺失之间存在连锁不平衡的可能性。本文的在线版本 (doi:10.1186/s13578-017-0149-3) 包含补充材料，可供授权用户使用。
Oculocutaneous albinism (OCA) is an autosomal recessive disorder. A significant portion of OCA patients has been found with a single pathogenic variant either in the TYR or the OCA2 gene. Diagnostic sequencing of the TYR and OCA2 genes is routinely used for molecular diagnosis of OCA subtypes. To study the possibility that genomic abnormalities with single or multiple exon involvement may account for a portion of the potential missing pathogenic variants (the second), we retrospectively analyzed the TYR gene by long range PCR and analyzed the target 2.7 kb deletion in the OCA2 gene spanning exon 7 in OCA patients with a single pathogenic variant in the target genes. In the 108 patients analyzed, we found that one patient was heterozygous for the 2.7 kb OCA2 gene deletion and this patient was positive with one pathogenic variant and one possibly pathogenic variant [c.1103C>T (p.Ala368Val) + c.913C>T (p.R305W)]. Further analysis of maternal DNA, and two additional OCA DNA homozygous for the 2.7 kb deletion, revealed that the phenotypically normal mother is heterozygous of the 2.7 kb deletion and homozygous of the p.R305W. The two previously reported patients with homozygous of the 2.7 kb deletion are also homozygous of p.R305W. Among the reported pathogenic variants, the pathogenicity of the p.R305W has been discussed intensively in literature. Our results indicate that p.R305W is unlikely a pathogenic variant. The possibility of linkage disequilibrium between p.R305W with the 2.7 kb deletion in OCA2 gene is also suggested. The online version of this article (doi:10.1186/s13578-017-0149-3) contains supplementary material, which is available to authorized users.