Identification of a novel DNMT1 mutation in a Chinese patient with hereditary sensory and autonomic neuropathy type IE

BACKGROUND: DNA methyltransferase 1 (EC 2.1.1.37), encoded by DNMT1 gene, is one of key enzymes in maintaining DNA methylation patterns of the human genome. It plays a crucial role in embryonic development, imprinting and genome stability, cell differentiation. The dysfunction of this group of enzymes can lead to a variety of human genetic disorders. Until now, mutations in DNMT1 have been found to be associated with two distinct phenotypes. Mutations in exon 20 of this gene leads to hereditary sensory and autonomic neuropathy type IE, and mutations in exon 21 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. CASE PRESENTATION: Here we report a novel DNMT1 mutation in a sporadic case of a Chinese patient with cerebellar ataxia, multiple motor and sensory neuropathy, hearing loss and psychiatric manifestations. Furthermore, we elucidated its pathogenic effect through molecular genetics studies and revealed that this defective DNMT1 function is responsible for the phenotypes in this individual. CONCLUSION: Our findings expand the spectrum of DNMT1-related disorders and provide a good example of precision medicine through the combination of exome sequencing and clinical testing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12883-018-1177-2) contains supplementary material, which is available to authorized users.