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

Abstract

This study was aimed to identify Fukutin (FKTN)-related congenital muscular dystrophies (CMD) with defective alpha-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 alpha-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 alpha-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.

• Authors: Bung Chan Lim, Chang-Seok Ki, Jong-Won Kim, Anna Cho, Min Jung Kim, Hee Hwang, Ki Joong Kim, Yong Seung Hwang, Woong Yang Park, Yun-Jung Lim, In One Kim, Jun Su Lee, Jong Hee Chae
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 20 Issue 8 Pg. 524-30 (Aug 2010) ISSN: 1873-2364 [Electronic] England
• PMID: 20620061 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• FKTN protein, human
• Membrane Proteins
• Dystroglycans
• DNA

Topics

• Brain (pathology)
• Child
• Child, Preschool
• DNA (genetics)
• DNA Mutational Analysis
• Dystroglycans (genetics, metabolism)
• Exons (genetics)
• Female
• Gene Frequency
• Glycosylation
• Heterozygote
• Homozygote
• Humans
• Immunohistochemistry
• Introns (genetics)
• Magnetic Resonance Imaging
• Male
• Membrane Proteins (genetics)
• Muscle, Skeletal (metabolism, pathology)
• Muscular Dystrophies (genetics, metabolism)
• Mutagenesis, Insertional
• Phenotype
• Republic of Korea (epidemiology)
• Reverse Transcriptase Polymerase Chain Reaction