腓骨肌萎缩症2A型一晚发家系临床表现及遗传学分析

Clinical and genetic analysis of one late-onset family with Charcot–Marie–Tooth type 2A:Case report

目的:分析晚发型常染色体显性遗传腓骨肌萎缩症(Charcot–Marie–Tooth,CMT)2A型征象病例的临床和遗传学特点。方法:采用家族谱系调查结合临床及基因检测进行整合分析。结果:先证者双侧臀部、双侧大腿肌群萎缩,双小腿后侧肌群明显萎缩,血清肌酸激酶值272 U/L,肌电图显示正中神经传导速度正常,双下肢神经源性损害(轴索为主)。基因检测发现MFN2基因外显子9的序列变异NM_014874:c.839G> A(p.R280H)杂合突变。先证者父亲存在外周神经-肌肉受累症状,母亲无临床症状。父亲携带相同杂合突变,母亲并未携带该突变。结论:家族谱系调查结合临床及基因检测是诊断晚发型CMT2A的可靠方法,有助于明确诊断不同类型的神经肌肉疾病。

Objective:To analyze the clinical and genetic characteristics of one late-onset family with Charcot–Marie–Tooth(CMT)type 2A.Methods:Pedigree survey combined with clinical and genetic testing was used for integrated analyses.Results:The proband showed muscle atrophy in both hips and thighs,especially in posterior sides of both legs.The value of serum creatine kinase was 272 U/L.Electromyography demonstrated that the median nerve conduction velocity was normal and the nerves of both lower extremities showed neurogenic damage(mainly axonal).Moreover,genetic testing revealed a heterozygous variant in exon 9 of the MFN2 gene NM_014874:c.839G>A(p.R280H).The father of the proband had similar peripheral neuromuscular symptoms and the same heterozygous mutation,while the mother did not show such clinical symptoms without genetic mutation.Conclusion:Pedigree investigation combined with clinical and genetic analysis is a reliable method for diagnosis of lateonset CMT2A and helpful to identify different neuromuscular diseases.