腓骨肌萎缩症2家系临床及遗传学分析

Clinical and genetic analysis of 2 families with Charcot-Marie-Tooth disease

目的 探讨腓骨肌萎缩症(CMT)的临床特点,并进行遗传学分析。方法 回顾性分析2个家系的临床资料。结果 家系1先证者双侧大腿及小腿后侧肌群萎缩,血清肌酸激酶292 U/L,EMG检查示上下肢周围神经损害(轴索为主)。基因检测发现先证者携带NEFH基因NM_02107:c.3057dupG:p.K1020Efs*43杂合突变。依据美国医学遗传学与基因组学学会(ACMG)规制评级为可能致病(Likely Pathogenic:PS3_moderate+PM2+PM4+PP1)。家系2先证者脊柱侧弯、小腿肌肉萎缩、扁平足,血肌酸激酶80 U/L,EMG检查示上下肢周围神经损害(轴索为主)。基因检测发现先证者携带MFN2基因NM_014874:c.746C>G:p.S249C杂合突变,该变异目前未见相关文献报道及收录,依据ACMG规制评级为可能致病(Likely Pathogenic:PM1+PM2+PM5+PP3)。结论 两个家系临床表现为肌无力伴肌肉萎缩、肌酸激酶正常或轻度升高、腱反射消失、弓形足、EMG提示神经源性损害,基因检测发现先证者分别携带NEFH、MFN2基因杂合突变。

Objective To investigate the clinical characteristics of Charcot-Marie-Tooth disease(CMT),and conduct genetic analysis.Methods The clinical data of 2 families were retrospectively analyzed.Results The proband of family 1 had atrophy of bilateral thigh and calf muscles,serum creatine kinase(CK)was 292 U/L,and EMG examination showed peripheral nerve damage of upper and lower limbs(mainly axonal).Genetic testing revealed that the proband carried a heterozygous mutation of NEFH:NM_02107:c.3057dupG:p.K1020Efs*43.According to American College of Medical Genetics and Genomics(ACMG),the variant of NEFH gene was interpreted as likely pathogenic(PS3_moderate+PM2+PM4+PP1).The proband of family 2 had scoliosis,calf muscle atrophy,flat foot,blood creatine kinase 80 U/L,and EMG examination showed peripheral nerve damage in the upper and lower limbs(mainly axonal).Genetic testing revealed that the proband carried a heterozygous mutation of the MFN2:NM_014874:c.746C>G:p.S249C.This mutation had not been reported and included in the relevant literature,and was likely to be pathogenic according to the ACMG regulation rating(Likely Pathogenic:PMI+PM2+PM5+PP3).Conclusions The clinical manifestations of the two families are muscle weakness with muscle atrophy,normal or mild elevation of creatine kinase,disappearance of tendon reflex,arched foot,and electromyography indicating neurogenic damage.Gene testing reveals that the probands carried heterozygous mutations in the NEFH and MFN2 genes,respectively.