Journal article
Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness
Annals of neurology, Vol.60(5), pp.597-602
2006
DOI: 10.1002/ana.20973
PMID: 17036286
Abstract
Objective: The fukutin gene (FKTN) is the causative gene for Fukuyama-type congenital muscular dystrophy, characterized by rather homogeneous clinical features of severe muscle wasting and hypotonia from early infancy with mental retardation. In contrast with the severe dystrophic involvement of skeletal muscle, cardiac insufficiency is quite rare. Fukuyama-type congenital muscular dystrophy is one of the disorders associated with glycosylation defects of alpha-dystroglycan, an indispensable molecule for intra-extra cell membrane linkage.
Methods: Protein and functional analyses of alpha-dystroglycan and mutation screening of FKTN and other associated genes were performed.
Results: Surprisingly, we identified six patients in four families showing dilated cardiomyopathy with no or minimal limb girdle muscle involvement and normal intelligence, associated with a compound heterozygous FKTN mutation. One patient died by rapid progressive dilated cardiomyopathy at 12 years old, and the other patient received cardiac implantation at 18 years old. Skeletal muscles from the patients showed minimal dystrophic features but have altered glycosylation of alpha-dystroglycan and reduced laminin binding ability. One cardiac muscle that underwent biopsy showed altered glycosylation of alpha-dystroglycan similar to that observed in a Fukuyama-type congenital muscular dystrophy patient.
Interpretation: FKTN mutations could cause much wider spectrum of clinical features than previously perceived, including familial dilated cardiomyopathy and mildest limb girdle muscular dystrophy.
Details
- Title: Subtitle
- Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness
- Creators
- Terumi MURAKAMI - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanYukiko K HAYASHI - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanKevin P CAMPBELL - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanMakiko OSAWA - Department of Pediatrics, Tokyo Women's Medical University, Tokyo, JapanIchizo NISHINO - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanSatoru NOGUCHI - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanMegumu OGAWA - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanIkuya NONAKA - Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Chiba, JapanYuzo TANABE - Department of Neurology, Kitasato University School of Medicine, JapanMieko OGINO - Division of Neurology, Chiba Children's Hospital, Chiba, JapanFumio TAKADA - Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, Kanagawa, JapanMakoto ERIGUCHI - Divisions of Neurology and Cardiovascular Medicine, Saga University Faculty of Medicine, Saga, JapanNorihiko KOTOOKA - Howard Hughes Medical Institute Research Laboratories, University of Iowa College of Medicine, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.60(5), pp.597-602
- Publisher
- Willey-Liss; Hoboken
- DOI
- 10.1002/ana.20973
- PMID
- 17036286
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020992902771
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