Wolfram综合征一家系的临床及遗传学分析

Clinical and genetic analysis of a pedigree with Wolfram syndrome

目的:研究由WFS1基因突变所导致的常染色体隐性遗传Wolfram综合征的临床特征和遗传学背景。方法:应用临床检查,基因分析和生物信息学方法研究一常染色体隐性遗传Wolfram综合征家系。结果:发现先证者及哥哥患糖尿病、色弱及视神经病变,此外其兄患尿崩症。全外显子组分析显示在兄弟二人的WFS1基因8号外显子存在两种杂合变异,即c.941G>A(p.W314X)和c.2309T>G(p.F770C),并在该家系中与临床表型共分离。结论:WFS1基因的复合杂合突变与该家系Wolfram综合征相关,其中c.941G>A(p.W314X)尚未见报道。

AIM:To investigate the clinical features and genetic background of autosomal recessive Wolfram syndrome caused by WFS1 gene mutation.METHODS:A pedigree with autosomal recessive Wolfram syndrome was studied by clinical examination,gene analysis and bioinformatics.RESULT:It was found that the proband and his brother had diabetes,color weakness and optic neuropathy.In addition,his brother had diabetes insipidus.Whole-exome sequencing(WES)analysis showed that there were two heterozygous variations in the WFS1 gene exon 8 of the two brothers:c.941G>A(p.W314X)and c.2309T>G(p.F770C),and were co-separated from the clinical phenotype in this family.CONCLUSION:The compound heterozygous mutation of WFS1 gene is associated with Wolfram syndrome in this pedigree.Among them,c.941G>A(p.W314X)has not been reported yet.