Molecular Genetic Analysis of Macular Corneal Dystrophy Patients from North India
Molecular Genetic Analysis of Macular Corneal Dystrophy Patients from North India
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DOI：
10.1159/000334911
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发表时间：
2012-01-01
影响因子：
2.1
通讯作者：
Vajpayee, Rasik B.
中科院分区：
文献类型：
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作者：
Paliwal, Preeti;Sharma, Arundhati;Vajpayee, Rasik B.
目的：确定北印度黄斑角膜营养不良 (MCD) 患者碳水化合物磺基转移酶 6 (CHST6) 基因的潜在遗传缺陷。方法：纳入21个家系的30例临床诊断的MCD患者和50名健康正常对照者作为研究对象。对患者进行详细的临床评估，然后对角膜组织进行组织病理学和超微结构研究。扩增血液样本中的 DNA 的 CHST6 编码区和上游区域，然后进行直接测序和计算机分析。结果：我们在来自 11 个家庭的 17 名患者中发现了致病突变。其中 4 个是新的（p.Ser54Tyr、p.Gln58Arg、p.Leu59His 和 p.Leu293Phe），2 个先前报道的（Arg93His 和 Glu274Lys）纯合子、1 个杂合终止密码子（p.Trp123X）和 2 个复合杂合子（p.Arg93His + p.Arg97Pro； p.Leu22Arg + p.Gln58X) 突变。还在 11 名患者中发现了错义单核苷酸多态性。如计算机分析所示，新突变是保守的。 13 名患者没有表现出任何致病性 CHST6 变化。结论：这是第一份关于北印度患者 MCD 分子分析的报告。所有病例都不能用 CHST6 突变来解释，这表明 MCD 可能是由于 CHST6 调控元件的其他变化或遗传异质性引起的。版权所有 (c) 2012 S. Karger AG，巴塞尔
Purpose: To identify underlying genetic defects in the carbohydrate sulfotransferase-6 (CHST6) gene in North Indian patients with macular corneal dystrophy (MCD). Methods: 30 clinically diagnosed MCD patients from 21 families and 50 healthy normal controls were recruited in the study. Detailed clinical evaluation in the patients was undertaken followed by histopathology and ultrastructural studies in corneal tissues. DNA from blood samples was amplified for the CHST6 coding and upstream region followed by direct sequencing and in silico analysis. Results: We identified pathogenic mutations in 17 patients from 11 families. Of these 4 were novel (p.Ser54Tyr, p.Gln58Arg, p.Leu59His and p.Leu293Phe), 2 were previously reported (Arg93His and Glu274Lys) homozygous, 1 heterozygous stop codon (p.Trp123X) and 2 compound heterozygous (p.Arg93His + p.Arg97Pro; p.Leu22Arg + p.Gln58X) mutations. A missense single-nucleotide polymorphism was also identified in 11 patients. The novel mutations were conserved as shown by in silico analysis. Thirteen patients did not show any pathogenic CHST6 changes. Conclusions: This is the first report on molecular analysis of MCD in North Indian patients. All cases could not be explained by mutations in CHST6, suggesting that MCD may result from other changes in the regulatory elements of CHST6 or from genetic heterogeneity. Copyright (c) 2012 S. Karger AG, Basel