Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is 
characterized by late onset (30-40 years old) cerebellar ataxia, sensory 
neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome 
sequencing in five individuals from three ADCA-DN kindreds and identified DNMT1 
as the only gene with mutations found in all five affected individuals. Sanger 
sequencing confirmed the de novo mutation p.Ala570Val in one family, and showed 
co-segregation of p.Val606Phe and p.Ala570Val, with the ADCA-DN phenotype, in 
two other kindreds. An additional ADCA-DN kindred with a p.GLY605Ala mutation 
was subsequently identified. Narcolepsy and deafness were the first symptoms to 
appear in all pedigrees, followed by ataxia. DNMT1 is a widely expressed DNA 
methyltransferase maintaining methylation patterns in development, and mediating 
transcriptional repression by direct binding to HDAC2. It is also highly 
expressed in immune cells and required for the differentiation of CD4+ into T 
regulatory cells. Mutations in exon 20 of this gene were recently reported to 
cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our 
mutations are all located in exon 21 and in very close spatial proximity, 
suggesting distinct phenotypes depending on mutation location within this gene.