Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Functional Assessment of Variants Associated with Wolfram Syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A Trans-ancestral Meta-Analysis of Genome-Wide Association Studies Reveals Loci Associated with Childhood Obesity

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Consortium-based genome-wide meta-analysis for childhood dental caries traits

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Altered surface expression of P2Y11 receptor with narcolepsy-associated mutations

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Type 1 narcolepsy is not present in 29 HPV-vaccinated individuals with subjective sleep complaints

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. DNMT1 regulates expression of MHC class i in post-mitotic neurons

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Juliane Winkelmann
  • Ling Lin
  • Barbara Schormair
  • Birgitte Rahbek Kornum
  • Juliette Faraco
  • Giuseppe Plazzi
  • Atle Melberg
  • Ferdinando Cornelio
  • Alexander E Urban
  • Fabio Pizza
  • Francesca Poli
  • Fabian Grubert
  • Thomas Wieland
  • Elisabeth Graf
  • Joachim Hallmayer
  • Tim M Strom
  • Emmanuel Mignot
View graph of relations

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.

Original languageEnglish
JournalHuman Molecular Genetics
Volume21
Issue number10
Pages (from-to)2205-10
Number of pages6
ISSN0964-6906
DOIs
Publication statusPublished - 15 May 2012

    Research areas

  • Amino Acid Sequence, Cerebellar Ataxia, DNA (Cytosine-5-)-Methyltransferase, Deafness, Exome, Exons, Genes, Dominant, Humans, Molecular Sequence Data, Mutation, Narcolepsy, Pedigree, Phenotype

ID: 45267026