MFN2基因新变异致腓骨肌萎缩症的家系分析

Identification of a novel variant of MFN2 gene in a pedigree with Charcot-Marie-Tooth disease

目的 对1腓骨肌萎缩症(CMT)家系进行全外显子基因测序,明确遗传学病因并总结临床特点。方法 收集该CMT家系的临床资料及外周血样,对先证者行神经电生理、全外显子基因测序等检查,筛查出致病基因位点后,应用Sanger测序技术对家系中其他成员的相同位点进行验证,并对该位点引起的蛋白质结构及功能改变进行分析。结果 该家系共9名成员,其中有3名受累,均为女性,起病年龄逐代提前。基因测序发现MFN2基因第8号外显子c.746C>T(p.Ser249Phe)杂合错义变异,该变异位点目前尚无报道,在正常人群数据库中频率极低,用两种软件预测出该变异对蛋白结构及功能产生影响,该变异在该家系成员中表型及基因型符合共分离现象,判定该变异可能致病。结论 MFN2基因c.746C>T(p.Ser249Phe)杂合错义变异,可能是该家系患者的致病原因,基因检测可以为临床诊断及遗传咨询提供帮助。

Objective To investigate the genetic etiology and clinical features of a Charcot-Marie-Tooth disease pedigree by whole exome sequencing.Methods The clinical data and peripheral blood samples of the CMT family were collected.The proband was examined by neuroelectrophysiology and whole exome sequencing.After the pathogenic gene locus was screened,Sanger sequencing technology was used to verify the same locus in other family members,and the changes in protein structure and function caused by the locus were analyzed.Results There were 9 members in this family,and 3 females were affected.The age of onset was advancing with generation.Gene sequencing identified a heterozygous missense mutation c.746C>T(p.Ser249Phe)in exon 8 of the MFN2 gene.This variant has not been reported so far,and its frequency is very low in the normal population database.The two software predicted that the variant would affect the structure and function of the protein.The phenotype and genotype of the variant were consistent with the co-segregation of the family members,and the variant was considered to be possibly pathogenic.Conclusion The heterozygous c.746C>T(p.Ser249Phe)variant of the MFN2 gene probably underlies the disease in this family.Gene detection can provide help for clinical diagnosis and genetic counseling.