Molecular Genetic Diagnosis of a Bethlem Myopathy Family with an Autosomal-Dominant COL6A1 Mutation, as Evidenced by Exome Sequencing.
BACKGROUND
We describe herein the application of whole exome sequencing (WES) for the molecular genetic diagnosis of a large Korean family with dominantly inherited myopathy.


METHODS
The affected individuals presented with slowly progressive proximal weakness and ankle contracture. They were initially diagnosed with limb-girdle muscular dystrophy (LGMD) based on clinical and pathologic features. However, WES and subsequent capillary sequencing identified a pathogenic splicing-site mutation (c.1056+1G>A) in COL6A1, which was previously reported to be an underlying cause of Bethlem myopathy. After identification of the genetic cause of the disease, careful neurologic examination revealed subtle contracture of the interphalangeal joint in the affected members, which is a characteristic sign of Bethlem myopathy. Therefore, we revised the original diagnosis from LGMD to Bethlem myopathy.


CONCLUSIONS
This is the first report of identification of COL6A1-mediated Bethlem myopathy in Korea, and indicates the utility of WES for the diagnosis of muscular dystrophy.
Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
Hyung Jun
HJ
Park
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Young Chul
YC
Choi
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Seung Min
SM
Kim
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Se Hoon
SH
Kim
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young Bin
YB
Hong
Department of Biological Science, Kongju National University, Gongju, Korea.
Bo Ram
BR
Yoon
Department of Biological Science, Kongju National University, Gongju, Korea. kwchung@kongju.ac.kr.
Ki Wha
KW
Chung
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. bochoi@skku.edu.
Byung Ok
BO
Choi
Bethlem myopathy; collagen type VI alpha 1 (COL6A1); whole exome sequencing