中国人Wolfram综合征WFS1基因的新突变

目的研究一个中国人Wolfram综合征患者家系中的WFS1基因突变情况。方法应用PCR-DNA直接测序对一个Wolfram综合征患者及家系成员的WFS1基因8个外显子及其侧翼内含子进行突变筛查;采用生物信息学方法对突变蛋白的结构与功能进行估测。结果发现外显子8第417位密码子发生缺失突变,即F417del。先证者为突变纯合子,其父母为姑表亲近亲结婚,均为突变杂合子。F417del突变位于跨膜区,失去了一个非极性氨基酸。生物信息学分析提示该突变可引起跨膜区二级结构改变并使突变蛋白疏水性下降。结论本研究发现的F417del突变是一个尚未报道过的Wolfram综合征新突变。

A novel mutation of WFS1 gene in Chinese patients with Wolfram syndrome

Objective Wolfram syndrome is an autosomal recessive disorder characterized by earlyonset diabetes mellitus, diabetes insipidus, optic atrophy and deafness. The aim of this study was to scan the WFS1 gene mutations in a Chinese Wolfram syndrome pedigree. Methods Eight exons and flanking introns of WFS1 gene were screened using PCR-DNA direct sequencing. Effects of the mutation on the structure and function of the WFS1 gene product, Wolframin, were evaluated by bioinformatics. Results A novel mutation, F417del, in the WFS1 gene was identified. The patient was homozygous of this mutation and the consanguineous parents were heterozygous. The mutation causes the lose of a non-polar amino acid , which was located in the transmembrane domain of the protein product. Bioinformatics predicted that the mutation altered the secondary structure of the transmembrane domain and decreased the hydrophobicity of F417del protein. Conclusions This study identified a novel mutation of WFS1 gene and represented the first cause of molecular characterization of Chinese Wolfram syndrome patients.