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Novel mutation in the methyltransferase domain of DNMT 1 in a hereditary sensory and autonomic neuropathy patient with hearing loss, cataract, and dementia
Author(s) -
Nishihara Hideaki,
Yuan Junhui,
Omoto Masatoshi,
Ogasawara Junichi,
Koga Michiaki,
Kawai Motoharu,
Higuchi Yujiro,
Hashiguchi Akihiro,
Takashima Hiroshi,
Kanda Takashi
Publication year - 2015
Publication title -
neurology and clinical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2049-4173
DOI - 10.1111/ncn3.145
Subject(s) - dna methyltransferase , genetics , medicine , mutation , missense mutation , hearing loss , exon , dementia , methyltransferase , biology , audiology , dna , gene , methylation , disease
DNMT 1 encodes DNA methyltransferase 1, which is a critical enzyme responsible for conversion of unmethylated DNA into hemimethylated DNA . To date, two phenotypes produced by DNMT 1 mutations have been reported, including hereditary sensory and autonomic neuropathy type IE , and autosomal dominant cerebellar ataxia, deafness and narcolepsy. We report a sporadic Japanese patient with dysautonomia, hearing loss, cataract, sensory disturbance and mild dementia. A novel missense mutation, c.4001C>T, was identified in exon 35, which encodes the methyltransferase domain of DNMT 1 . Until now, all reported mutations of DNMT 1 were within the replication focus targeting sequence domain of DNA methyltransferase 1. This is the first report of a mutation in the methyltransferase domain of DNA methyltransferase 1. Our patient showed remarkable autonomic dysfunction along with cataract, a possible new phenotype of DNMT 1 mutations.