一例MEGDEL综合征患儿的临床及遗传学分析

Clinical and molecular genetic analysis of a case of MEGDEL syndrome

目的探讨1例MEGDEL综合征患儿的临床及基因变异特点。方法收集患儿的临床资料,采集患儿及其父母的外周血样,应用二代测序技术对患儿进行线粒体基因组及全外显子组分析,用Sanger测序以及荧光定量PCR验证候选变异及其来源。结果患儿为男性,2岁6个月,主要表现为新生儿期低血糖、智力运动发育落后伴倒退。头颅磁共振成像显示双侧壳核损害,提示为Leigh综合征。尿有机酸检测提示3-甲基戊烯二酸水平轻度增高。全外显子测序发现患儿SERAC1基因存在第6~17外显子杂合缺失以及c.307A>T杂合无义变异,分别遗传自表型正常的父母,确诊为MEGDEL综合征。给予左卡尼汀、维生素B1、维生素B_(2)、辅酶Q_(10)、巴氯芬、葡醛内酯片等治疗后睡眠及精神状态较前好转。结论确诊了1例不伴耳聋的MEGDEL综合征患儿。无义变异和大片段缺失两种变异既往均未见报道,扩大了SERAC1基因的变异谱。

Objective To explore the clinical and genetic characteristics of a child with MEGDEL syndrome.Methods Clinical data of the child was reviewed.Peripheral blood samples of the child and his parents were collected.Mitochondrial genome and the whole exome of the child were analyzed by next-generation sequencing.Candidate variant and its origin were verified by Sanger sequencing and fluorescence quantitative PCR.Results The patient,a 2-year-and-6-month-old male,has featured hypoglycemia,mental and motor retardation with regression.Cranial MRI showed bilateral putamen damage suggestive of Leigh syndrome.Test of urine organic acid indicated that the level of 3-methylpentenoic acid was slightly increased.Whole exome sequencing revealed that the child has harbored heterozygous deletion of exons 6 to 17 and c.307A>T nonsense variant of the SERAC1 gene,which were respectively inherited from his parents who were asymptomatic.Treatment with Levocarnitine,vitamin B1,vitamin B_(2),coenzyme Q_(10),baclofen and glucuronolactone resulted in improvement of sleep and mental state.Conclusion A case of MEGDEL syndrome without deafness was diagnosed.Discovery of the nonsense mutation and large fragment deletion have enriched the spectrum of SERAC1 gene variants.