Analysis of DYSF gene mutations in two pedigrees affected with limb-girdle muscular dystrophy type 2BCSCD

Objective: To analyze mutations of DYSF gene in two pedigrees affected with limb-girdle muscular dystrophy 2B (LGMD-2B). Methods: Genomic DNA was extracted from peripheral blood samples of the two probands and unaffected family members. Variant sites were screened by next-generation sequencing using gene panel as well as Sanger sequencing. Results: Four pathogenic mutations of the DYSF gene were detected, which included a de novo mutation and three mutations with uncertain significance. In pedigree 1, the proband carried compound heterozygous mutations of c. 1667T>C (p. Leu556Pro) and c. 5567T>A (p. Vall856Glu), which were respectively inherited from her mother and father. Proband of pedigree 2 carried compound heterozygous mutations of c. 4853A>G (p. Tyrl618Cys) and c. 4876G> A (p. Vall612Ile), among which c. 4876G> A (p. Vall626Ile) was also found in his father and grandfather, while c. 4853A>G (p. Tyrl618Cys) was detected in his mother and grandmother. Conclusion: The two compound heterozygous mutations of the DYSF gene probably underlie the LGMD2B in the two pedigrees. Next generation sequencing has conferred great advantage for gene diagnosis of hereditary myopathy. © 2018 MeDitorial Ltd. All rights reserved.