Analysis on clinical phenotype and gene mutation of two cases of limb - girdle muscular dystrophy type 2A during preclinical stage

Abstract

Objective To explore the clinical manifestations, laboratory examination, imaging, neurophysiological, genetic test and family data of 2 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) during the preclinical stage, and to provide clinical data for the early diagnosis of LGMD2A. Methods and Results Two 4-year-old male patients presented elevated serum creatine kinase (CK) level (25-fold and 60-fold higher than normal levels, respectively), with good motor function. Case 1 had skin damage performance of repeated multiple rashes and mild increased back hair. In Case 2, the patient's double lower legs were slightly enlarged and firm, and EMG and muscle biopsies showed myogenic damage. There was no abnormality in MRI of double thigh muscles. The next-generation sequencing (NGS) showed that there were complex heterozygous mutations in the CAPN3 gene in both cases: Case 1 carried missense [c.2092C > T (p.Arg606Ser)] and frameshift [c.712delT (p.Phe239LeufsTer14)] compound heterozygous mutation and none of the mutations have been reported; Case 2 carried compound heterozygous missense mutations [c.600C > G (p.Phe200Leu) and c.619A > G (p.Lys207Glu)], and the former has not been reported. Sanger sequencing confirmed that the pedigree was autosomal recessive. The clinical diagnosis was LGMD2A, and their families were diagnosed as LGMD2A pedigree. Conclusions The possibility of LGMD2A needs to be considered for asymptomatic high CK. In addition, this study increased the diversity of CAPN3 gene mutations in the population.

DOI: 10.3969/j.issn.1672-6731.2018.07.007