DNMT1 mutation hot spot causes varied phenotypes of HSAN1 with dementia and hearing loss.

ABSTRACT:

Background

Mutations in DNA methyltransferase 1 (DNMT1) have been identified in 2 autosomal dominant syndromes: 1) hereditary sensory autonomic neuropathy with dementia and hearing loss (HSAN1E); and 2) cerebellar ataxia, deafness, and narcolepsy. Both syndromes have mutations in targeting sequence (TS) domain (exons 20-21), which is important in mediating DNA substrate binding to the DNMT1 catalytic domain. Frontal lobe hypometabolism has been documented in an HSAN1E family, but memory loss has been the primary cognitive complaint. The chromosomal location of the DNMT1 gene at 19p13.2 has been linked to familial late-onset Alzheimer disease.

Methods

We sequenced 41 exons of DNMT1 and their flanking regions in 1) 2 kindreds with HSAN1E; 2) 48 patients with HSAN1 alone withou

SUBMITTER: Klein CJ 

PROVIDER: S-EPMC3598458 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature