산성 알파 글루코시다아제가 감소한 근육병에서 Whole Exome Sequencing을 이용한 DYSF 유전자 복합이형접합돌연변이의 규명

Abstract

Background: This study was designed to identify the genetic cause in myopathy family with decreased acid-alpha glucosidase activity.

Methods: Clinical and laboratory features of two affected family members were analyzed. Then, whole exome sequencing (WES) was performed.

Results: The proband (a 54-year-old woman) and her sister (a 57-year-old woman) presented to our neurologic clinic with proximal muscle weakness. They recalled very active and sporty life since adolescence. At the late teens, they first noticed difficulty in climbing stairs. Neurological examination revealed muscle weakness and atrophies of proximal muscles, predominantly at lower limbs. Electromyography revealed chronic myopathic finding and serum creatine kinase level was elevated in the proband. In addition, serum acid-alpha glucosidase activities were decreased in two patients. WES identified compound heterozygous mutations (c.5713C>T and c.937+1G>A) in DYSF, which were previously reported to be an underlying cause of limb-girdle muscular dystrophy 2B.

Conclusions: We identified compound heterozygous DYSF mutations in a myopathy family with decreased acid-alpha glucosidase activity. This result demonstrated the usefulness of WES for the diagnosis of limb-girdle muscular dystrophy.