title: Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.
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.
  
  
  CONCLUSIONS
  FKTN mutations could cause much wider spectrum of clinical features than previously perceived, including familial dilated cardiomyopathy and mildest limb girdle muscular dystrophy.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.|Department of Pediatrics, Tokyo Women's Medical University, Tokyo.
authors.forename: Terumi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.|Department of Pediatrics, Tokyo Women's Medical University, Tokyo.
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.
authors.forename: Megumu
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.affiliation: Division of Neurology, Chiba Children's Hospital, Chiba.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Department of Neurology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Ogino
authors.affiliation: Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Takada
authors.affiliation: Division of Neurology, Saga University Faculty of Medicine, Saga, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Eriguchi
authors.affiliation: Division of Cardiovascular Medicine, Saga University Faculty of Medicine, Saga, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kotooka
authors.affiliation: Howard Hughes Medical Institute Research Laboratories, University of Iowa College of Medicine, Iowa City, IA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University, Tokyo.
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D049030:Dystroglycans / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D018908:Muscle Weakness / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017354:Point Mutation / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D049030:Dystroglycans