Wolfram综合征一例中国患者WFS1基因的两个新突变

Two novel mutations of WFS1 gene in a Chinese family with Wolfram syndrome

目的研究1例中国人Wolfram综合征患者家系中的WFS1基因突变情况。方法应用聚合酶链反应-脱氧核糖核酸(PCR-DNA)直接测序对1例Wolfram综合征患者及其家系成员的WFS1基因8个外显子及其侧翼内含子进行突变筛查。结果发现外显子8第434位密码子发生缺失突变(V434del)及第666位密码子突变为终止子(W666X)。先证者存在这两个位点的复合突变,家族其他成员中,3人是V434del突变的杂合子,另有3人是W666X突变的杂合子。结论本研究发现的V434del及W666X突变均为尚未报道过的Wolfram综合征的新突变。

Objective To investigate WFS1 gene mutations in a Chinese Wolfram syndrome pedigree. Methods Eight exons and flanking introns of WFS1 gene were screened in the Wolfram syndrome patient using PCR- DNA direct sequencing. Results Two novel mutations, V434del and W666X, in the WFS1 gene were identified. The patient was homozygous of this mutation and the consanguineous parents were heterozygous. The compound heterozygous mutation of V434del and another compound heterozygous mutationW666X in exon 8 of WFS1 gene were identified in the present patient. Three patients with heterozygotes had been found with V434del mutation and the other three with W666X mutation in the whole family. Conclusions The novel mutation of VVFS 1 gene in this study is the first report of WFS with the mutation V434del and W666X in the WFS1 gene in a Chinese family. （Shanghai IVied J, 2009, 32： 431-433）