关键词: 肌营养不良，肢带型, 肌无力, 肌酸激酶, 全外显子组测序, 病例报告

Abstract:

Limb-girdle type muscular dystrophy is a group of muscle myopathies with the progressive muscle change mainly in the pelvic girdle and shoulder girdle. It often occurs in childhood with obvious genetic heterogeneity. We reported a case of limb-girdle type muscular dystrophy that a child was diagnosed firstly as bronchopneumonia. The whole exome sequencing technology was used to screen the variant sites of related genes, Sanger sequencing technology was used to analyze and verify the suspected variant sites. The child was found to have the compound heterozygous mutations of DYSF gene (NM_003494), a c.2974T>C(p.W992R) mutation in exon 12 and a c.1169A>G(p.D390G) mutation in exon 28. The locus c.2974T>C(p.W992R) was inherited from the father, and the locus c.1169A>G(p.D390G) from the mother. Both variants were the truncating variants (PVS1). They were not included in the gene database of normal population, so they were rare variants (PM2_Supporting). Therefore, both variants were assessed as the likely pathogenic variants. The validation results of Sanger sequencing were consistent with the results of whole exome sequencing. Accordingly, the child was finally diagnosed as limb-girdle muscular dystrophy type 2B. Whole exome sequencing technology can provide genetic analysis and prenatal diagnosis for limb-girdle type muscular dystrophy, and has key value in clinical decision-making, genetic counseling and re-pregnancy planning.

Key words: Muscular dystrophies, limb-girdle, Muscle weakness, Creatine kinase, Whole exome sequencing, Case reports