肢带型肌营养不良症2B型家系的临床表型和基因型分析

Clinical phenotype and genotype analysis of a pedigree with limb band muscular dystrophy type 2B

目的研究肢带型肌营养不良家系的临床资料,鉴定Dysferlin基因(DYSF)的突变并分析基因型和临床表型的关联。方法回顾性分析先证者临床症状,收集并对其家系进行临床表型分析,分别获取其家系成员的外周血,提取DNA,采用高通量二代测序和Sanger测序检测家系重要成员DYSF的突变情况。结果家系中先证者及其二弟为肢带型肌营养不良患者,起病年龄分别为20岁及5岁,呈进行性加重,表现为双上肢和双大腿肌萎缩,肌酸激酶明显升高,肌酸激酶同工酶中度升高;肌电图示肌源性损害改变。DYSF基因检测共发现2个致病突变,先证者及其二弟的DYSF存在c.268C>T(p.Arg90Ter;母亲去世)以及c.3214C>T(p.Arg1072Trp;遗传自父亲)复合杂合突变。结论该家系肢带型肌营养不良发病原因为DYSF基因的复合杂合突变所致,基因测序分析是对疑似病例进行确诊分型的有效方法。

Objective To study the clinical data of a pedigree with limb band muscular dystrophy,identify the DYSF gene mutation and analyze the relationship between genotype and clinical phenotype.Methods The clinical symptoms of the proband were analyzed retrospectively,and the clinical phenotypes of the proband family were collected and analyzed.DNA was extracted from peripheral blood of the family members.The mutation of DYSF gene was detected by next-generation sequencing and Sanger sequencing.Results The proband and his second brother are the patients of the disease.The onset age of the two patients was 20 and 5 years old,respectively,with progressive aggravation,manifesting muscle atrophy of both upper limbs and thighs,marked elevation of creatine kinase,moderate elevation of creatine kinase isoenzyme,and myoelectric diagram of myogenic damage.Two pathogenic mutations were found in DYSF gene detection.The compound heterozygous mutation c.268 C>T(p.Arg90 Ter;mother died)and c.3214 C>T(p.Arg1072 Trp;inherited from father)were found in the DYSF gene of the proband and his second brother.Conclusion In this family,compound heterozygous mutations in the DYSF lead to limb band muscular dystrophy 2 B.Gene sequencing analysis can be used to identify and classify suspected cases.