Novel mutation in the methyltransferase domain of DNMT 1 in a hereditary sensory and autonomic neuropathy patient with hearing loss, cataract, and dementia

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.