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.

KEYWORDS : Limb-girdle muscular dystrophy, DYSF, Glycogen storage disease type II, Whole exome sequencing