title: Japanese family with an autosomal dominant chromosome instability syndrome: a new neurodegenerative disease?
abstract: We report on a Japanese family having an autosomal dominant neurodegenerative disease with chromosomal instability and radiosensitivity. Clinical manifestations of affected members included short stature, osteoporosis, severe dental caries, and various neurological abnormalities, such as mental retardation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demonstrated a markedly atrophic spinal cord and degeneration of the white matter. Cytogenetic examination showed spontaneous chromosome rearrangements at 14q11.2 and hypersensitivity to radiation and bleomycin. The degree of these cytogenetic abnormalities was significantly higher in the patients than in normal controls but lower than in patients with ataxia telangiectasia or Nijmegen breakage syndrome. Moreover, genetic anticipation was observed in this family: the age of disease onset became earlier, MRI abnormalities more extensive, and the chromosome hypersensitivity to radiation increased in successive generations. We speculate that a basic defect in this family is a mutation in the gene that is responsible for DNA double-strand breakage repair.
authors.affiliation: Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto, Japan. y-takei@hsp.md.shinshu-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: T
authors.initials: T
authors.lastname: Tokuda
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Wakui
authors.forename: S
authors.initials: S
authors.lastname: Matsuura
authors.forename: S
authors.initials: S
authors.lastname: Ohara
authors.forename: Y
authors.initials: Y
authors.lastname: Sekijima
authors.forename: E
authors.initials: E
authors.lastname: Hidaka
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
authors.forename: H
authors.initials: H
authors.lastname: Shigeta
authors.forename: K
authors.initials: K
authors.lastname: Komatsu
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D011995:Recombination, Genetic; D013577:Syndrome