近亲婚配致WDR73纯合突变相关Galloway-Mowat综合征家系基因检测及生物信息学分析

Gene detection and bioinformatics analysis of Galloway-Mowat syndrome associated with homozygous mutation of WDR73 caused by consanguineous marriage

背景Galloway-Mowat综合征是一种罕见的常染色体隐性遗传神经退行性疾病,多发生于父母为近亲婚配的家庭,国内报道较少。目的通过分析1例近亲婚配致WDR73纯合突变相关的Galloway-Mowat综合征患儿及其家系基因特点,了解该病遗传学特征。方法收集解放军总医院第一医学中心儿科2021年10月收治的1例Galloway-Mowat综合征患儿及其家族临床资料,对患儿及其父母外周血进行全外显子基因检测,并对部分家族成员进行一代测序验证。结果患儿男,11月龄,于3月龄发现不能追视,并伴精神运动发育落后。视觉诱发电位提示双眼视神经传导功能重度阻滞,头颅MRI显示胼胝体薄,侧脑室前脚变钝,髓鞘化延迟。基因检测发现WDR73基因纯合移码突变c.972_973dup(p.F325Sfs*10),明确诊断为Galloway-Mowat综合征。患儿父母为近亲结婚,父母为该基因突变位点携带者。结论本研究扩展了Galloway-Mowat综合征的基因谱。近亲婚配会增加隐性遗传病的发病率。

Background Galloway–Mowat syndrome is a rare autosomal recessive neurodegenerative disease.It is reported that it mostly occurs in families where parents are consanguineous,but there are few reports in China.Objective To understand the genetic features of Galloway-Mowat syndrome by analyzing the genetic characteristics of a child associated with homozygous mutation of WDR73 caused by consanguineous marriage and his pedigree.Methods Clinical data about a child with Galloway-Mowat syndrome and his family admitted to the Department of Pediatrics of the First Medical Center of Chinese PLA General Hospital in October 2021 were collected.The whole exon gene was detected in the peripheral blood of the patient and his parents,and part of the family members were verified by one generation sequencing.Results At the age of 3 months,the infant presented poor chasing and psychomotor development.Visual evoked potentials suggested severe obstruction of the optic nerve conduction in both eyes,head MRI showed a thin corpus callosum,blunt anterior horn of the lateral ventricle and delayed myelination.A homozygous frameshift mutation was found in WDR73 gene c.972_973dup(p.F325Sfs*10).The diagnosis of Galloway-Mowat syndrome was confirmed.The parents of the boy were consanguineous and they were carriers of the gene mutation site.Conclusion In this study,we have extended the gene spectrum of Galloway-Mowat syndrome,and the WDR73 gene frameshift mutation is a pathogenic mutation.Consanguineous marriage will increase the incidence of recessive genetic diseases.