Analysis of DYSF gene mutations in two pedigrees affected with limb-girdle muscular dystrophy type 2B / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To analyze mutations of DYSF gene in two pedigrees affected with limb-girdle muscular dystrophy 2B (LGMD-2B).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>