Fukutin mutations in congenital muscular dystrophies with defective glycosylation of dystroglycan in Korea

Lim, Bung Chan; Ki, Chang-Seok; Kim, Jong-Won; Cho, Anna; Kim, Min Jung; Hwang, Hee; Kim, Ki Joong; Hwang, Yong Seung; Park, Woong Yang; Lim, Yun-Jung; Kim, In One; Lee, Jun Su; Chae, Jong Hee

doi:10.1016/j.nmd.2010.06.005

« Previous Next »Neuromuscular Disorders
Volume 20, Issue 8 , Pages 524-530, August 2010

Fukutin mutations in congenital muscular dystrophies with defective glycosylation of dystroglycan in Korea

Bung Chan Lim
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
- These authors contributed equally to this work.
Chang-Seok Ki
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- These authors contributed equally to this work.
Jong-Won Kim
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Anna Cho
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Min Jung Kim
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Hee Hwang
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Ki Joong Kim
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Yong Seung Hwang
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Woong Yang Park
- Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea
Yun-Jung Lim
- Department of Radiology, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
In One Kim
- Department of Radiology, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Jun Su Lee
- Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, South Korea
Jong Hee Chae
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
- Corresponding author. Address: Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-Gu, Seoul 110-744, South Korea. Tel.: +82 2 2072 3622; fax: +82 2 743 3455.

Received 16 April 2010; received in revised form 27 May 2010; accepted 9 June 2010.

Abstract

This study was aimed to identify Fukutin (FKTN)-related congenital muscular dystrophies (CMD) with defective α-dystroglycan glycosylation in Korea and to discuss their genotype–phenotype spectrum focusing on detailed brain magnetic resonance imaging (MRI) findings. FKTN mutations were found in nine of the 12 CMD patients with defective α-dystroglycan glycosylation patients (75%). Two patients were homozygous for the Japanese founder retrotransposal insertion mutation. Seven patients were heterozygous for the retrotransposal insertion mutation, five of whom carried a novel intronic mutation that activates a pseudoexon between exons 5 and 6 (c.647+2084G>T). Compared with individuals that were homozygous for the retrotransposal insertion mutation, the seven heterozygotes for the retrotransposal insertion mutation, including five patients with the novel pseudoexon mutation, exhibited a more severe clinical phenotype in terms of motor abilities and more extensive brain MRI abnormalities (i.e., a wider distribution of cortical malformation and pons and cerebellar hypoplasia). FKTN mutations are the most common genetic cause of CMD with defective α-dystroglycan glycosylation in Korea. Compound heterozygosity of the retrotransposal insertion and the novel pseudoexon mutation is the most prevalent genotype in Korea and is associated with a more severe clinical and radiological phenotype compared with homozygosity for the retrotransposal insertion mutation.

Keywords: Muscular dystrophy, Congenital, Mutation, Dystroglycan