Japanese family with an autosomal dominant chromosome instability syndrome: A new neurodegenerative disease?

We report on a Japanese family having an autosomal dominant neurodegenerati ve disease with chromosomal instability and radiosensitivity. Clinical mani festations of affected members included short stature, osteoporosis, severe dental caries, and various neurological abnormalities, such as mental reta rdation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demons trated a markedly atrophic spinal cord and degeneration of the white matter . Cytogenetic examination showed spontaneous chromosome rearrangements at 1 4q11.2 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 N ijmegen breakage syndrome. Moreover, genetic anticipation was observed in t his family: the age of disease onset became earlier, MRI abnormalities more extensive, and the chromosome hypersensitivity to radiation increased in s uccessive generations. We speculate that a basic defect in this family is a mutation in the gene that is responsible for DNA double-strand breakage re pair. Am. J. Med. Genet. 94:265-270, 2000. (C) 2000 Wiley-Liss, Inc.