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

To analyze mutations of DYSF gene in two pedigrees affected with limb-girdle muscular dystrophy 2B (LGMD-2B).

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.

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 to C (p.Leu556Pro) and c.5567T to A (p.Val1856Glu), which were respectively inherited from her mother and father. Proband of pedigree 2 carried compound heterozygous mutations of c.4853A to G (p.Tyr1618Cys) and c.4876G to A (p.Val1612Ile), among which c.4876G to A (p.Val1626Ile) was also found in his father and grandfather, while c.4853A to G (p.Tyr1618Cys) was detected in his mother and grandmother.

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.