Clinical and molecular genetic study of limb-girdle muscular dystrophy type 2A in a Chinese family / 中华实用儿科临床杂志

ABSTRACT

Objective To analyze the clinical,muscle pathological features and molecular mutations in the 2 Chinese Han siblings with limb-girdle muscular dystrophy(LGMD) and conclude the phenotype/genotype correlations.Methods Clinical and muscle pathological data were collected.Genomic DNA of the two siblings and their parents were extracted using standard procedures from the peripheral leukocytes.A custom of targeted gene panel including 61 neuromuscular genes were designed by using the Agilent Sureselect Target Enrichment Kit.Targeted next generation sequencing(NGS) was performed in the proband,and CAPN3 gene mutation was verified with Sanger sequencing in the two siblings and their parents.The dbSNP138 and http//www.dmd.nl were searched to determine the disease-causing mutations.Results The proband slowly showed muscle weakness profoundly with pelvic muscles,developed difficulty in squatting and standing and climbing stairs.She had a tight Achilles tendon,high CK level (1 908-9 241 IU/L),without winging scapula and hypertrophy calf.The affected brother was only diagnosed hyper CKemia.By using the targeted NGS,the two siblings possessed the same two compound heterozygous mutations(c.717delT and c.2243G ＞ A) in CAPN3 gene.The two mutations both were verified by Sanger sequencing and had been reported before.Conclusions LGMD is clinically and genetically heterogeneous,and targeted NGS is powerful in defining the causal mutation of LGMD and helpful in investigating the exact genotype/phenotype analysis.