NoVSX1 gene mutations associated with keratoconus
NoVSX1 gene mutations associated with keratoconus
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DOI：
10.1167/iovs.05-1530
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Rabinowitz, YS
中科院分区：
文献类型：
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作者：
Aldave, AJ;Yellore, VS;Rabinowitz, YS
目的.目的探讨VSX1基因突变是否在圆锥角膜（KTCN）的发生发展中起作用。对100例诊断为KTCN.CTTS的临床和局部特征的无关患者进行DNA提取、PCR扩增和VSX1基因直接测序。在之前确定的VSX1基因中的四种假定致病突变（Leu17Pro、Asp144Glu、Leu159Met和Arg166Trp）中，仅在单个受影响患者中确定了Asp144Glu。鉴定了两种新的单核苷酸多态性（SNP），其均导致同义替换：c. 4例患者为53G > T（Ser6Ser），c. 209G > T（Pro58Pro）。还鉴定了两个先前报道的SNP：c. 426C > A（Arg131Ser），以及c. 581A > G（Ala 182Ala）51例。在受影响患者队列的单个成员中，仅确定了VSX1基因中的一种假定致病突变Asp144Glu。然而，如前所述，Asp144Glu是一种非致病性多态性。在大量不相关的KTCN患者中VSX1基因中没有致病性突变，表明其他遗传因素参与了这种疾病的发展。
PURPOSE. To determine whether mutations of the VSX1 gene play a pathogenetic role in the development of keratoconus (KTCN).METHODS. DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN.RESULTS. Of the four previously identified presumed pathogenic mutations in the VSX1 gene (Leu17Pro, Asp144Glu, Leu159Met, and Arg166Trp), only Asp144Glu was identified in a single affected patient. Two novel single nucleotide polymorphisms (SNPs), both resulting in synonymous substitutions, were identified: c. 53G > T (Ser6Ser) in four affected patients and c. 209G > T (Pro58Pro) in two affected patients. Two previously reported SNPs were also identified: c. 426C > A (Arg131Ser) in one affected patient and c. 581A > G (Ala182Ala) in 51 of the 100 affected patients.CONCLUSIONS. Only one of the presumed pathogenic mutations in the VSX1 gene, Asp144Glu, was identified in a single member of the cohort of affected patients. However, as previously demonstrated, Asp144Glu is a non-disease-causing polymorphism. The absence of pathogenic mutations in the VSX1 gene in a large number of unrelated KTCN patients indicates that other genetic factors are involved in the development of this disorder.