Novel mutation in the methyltransferase domain of DNMT1 in a hereditary sensory and autonomic neuropathy patient with hearing loss, cataract, and dementia

DNMT1 encodes DNA methyltransferase 1, which is a critical enzyme responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 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 DNMT1. Until now, all reported mutations of DNMT1 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 DNMT1 mutations.