title: Congenital fiber type disproportion myopathy caused by LMNA mutations.
abstract: A boy, who had shown muscle weakness and hypotonia from early childhood and fiber type disproportion (FTD) with no dystrophic changes on muscle biopsy, was initially diagnosed as having congenital fiber type disproportion (CFTD). Subsequently, he developed cardiac conduction blocks. We reconsidered the diagnosis as possible LMNA-myopathy and found a heterozygous mutation in the LMNA gene. This encouraged us to search for LMNA mutations on 80 patients who met the diagnostic criteria of CFTD with unknown cause. Two patients including the above index case had heterozygous in-frame deletion mutations of c.367_369delAAG and c.99_101delGGA in LMNA, respectively. Four of 23 muscular dystrophy patients with LMNA mutation also showed fiber type disproportion (FTD). Importantly, all FTD associated with LMNA-myopathy were caused by hypertrophy of type 2 fibers as compared with age-matched controls, whereas CFTD with mutations in ACTA1 or TPM3 showed selective type 1 fiber atrophy but no type 2 fiber hypertrophy. Although FTD is not a constant pathological feature of LMNA-myopathy, we should consider the possibility of LMNA-myopathy whenever a diagnosis of CFTD is made and take steps to prevent cardiac insufficiency.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kajino
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Ishihara
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishigaki
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
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, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
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, Japan; Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurophysiology, Tokyo Medical University, Tokyo, Japan. Electronic address: yhayashi@tokyo-med.ac.jp.
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
mesh_terms: D000199:Actins / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000473:pathology; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology; D009243:NAD / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C494847:LMNA protein, human; D034904:Lamin Type A; D009243:NAD
keywords: ACTA1; CFTD; Fiber type disproportion (FTD); LMNA-myopathy; TPM3; congenital myopathy; muscular dystrophy