Japanese family with an autosomal dominant chromosome instability syndrome: a new neurodegenerative disease?
| Autor: | Keiko Wakui, Kunihiro Yoshida, M. Ishikawa, Shinya Matsuura, Takahiko Tokuda, Hiroaki Shigeta, Shozo Ishikawa, Shu-ichi Ikeda, Shinji Ohara, Eiko Hidaka, Yoshimitsu Fukushima, Kenji Komatsu, Yoshiki Sekijima |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Hyperreflexia Biology Short stature Muscular Atrophy Spinal Japan Chromosome instability medicine Humans Genetics (clinical) Genes Dominant Genetics Chromosome Aberrations Recombination Genetic Infant Neurodegenerative Diseases Chromosome Fragility Syndrome Middle Aged medicine.disease Magnetic Resonance Imaging Pedigree Anticipation (genetics) Ataxia-telangiectasia Female medicine.symptom Chromosome instability syndrome Nijmegen breakage syndrome |
| Zdroj: | American journal of medical genetics. 94(4) |
| ISSN: | 0148-7299 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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