MEF2C基因变异所致NEDHSIL患儿2例的临床及遗传学分析

Clinical and genetic analysis of two children with Neurodevelopmental disorder with hypotonia,stereotypic hand movements,and impaired language due to de novo variants of MEF2C gene

目的探讨2例NEDHSIL患儿的临床特征及其遗传学病因,为其遗传咨询提供依据。方法选取2021年10月15日于宁波市妇女儿童医院就诊的2例患儿为研究对象。采用全外显子组测序(WES)技术对患儿进行检测,针对可疑变异进行Sanger测序验证与致病性分析。结果患儿1携带MEF2C基因c.138delC(p.Ile47Serfs*42)杂合新发变异,患儿2携带MEF2C基因c.833del(p.L278*)杂合新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南,MEF2C基因c.138delC和c.833del变异均评为致病性变异(PVS1+PS2+PM2_Supporting)。结论MEF2C基因c.138delC和c.833del变异可能分别为2例NEDHSIL患儿的致病原因,丰富了MEF2C基因的变异谱,为家系的遗传咨询提供了依据。

Objective To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia,stereotypic hand movements,and impaired language(MEDHSIL).Methods Two children who had visited the Ningbo Women and Children's Hospital on October 15,2021 were selected as the study subjects.Whole exome sequencing(WES)was carried out for both patients.Candidate variants were verified by Sanger sequencing of their family members.Results The two children were respectively found to harbor a heterozygous c.138delC(p.Ile47Serfs*42)variant and a c.833del(p.L278*)variant of the MEF2C gene.Neither variant was detected in their parents.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were predicted to be pathogenic(PVS1+PS2+PM2_Supporting).Conclusion The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children.Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.