PMID- 22328086
OWN - NLM
STAT- MEDLINE
DCOM- 20120913
LR  - 20220408
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 21
IP  - 10
DP  - 2012 May 15
TI  - Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and 
      narcolepsy.
PG  - 2205-10
LID - 10.1093/hmg/dds035 [doi]
AB  - 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.
FAU - Winkelmann, Juliane
AU  - Winkelmann J
AD  - Institute of Human Genetics, Technische Universitat Munchen, Munich 81675, 
      Germany.
FAU - Lin, Ling
AU  - Lin L
FAU - Schormair, Barbara
AU  - Schormair B
FAU - Kornum, Birgitte R
AU  - Kornum BR
FAU - Faraco, Juliette
AU  - Faraco J
FAU - Plazzi, Giuseppe
AU  - Plazzi G
FAU - Melberg, Atle
AU  - Melberg A
FAU - Cornelio, Ferdinando
AU  - Cornelio F
FAU - Urban, Alexander E
AU  - Urban AE
FAU - Pizza, Fabio
AU  - Pizza F
FAU - Poli, Francesca
AU  - Poli F
FAU - Grubert, Fabian
AU  - Grubert F
FAU - Wieland, Thomas
AU  - Wieland T
FAU - Graf, Elisabeth
AU  - Graf E
FAU - Hallmayer, Joachim
AU  - Hallmayer J
FAU - Strom, Tim M
AU  - Strom TM
FAU - Mignot, Emmanuel
AU  - Mignot E
LA  - eng
GR  - P50 NS023724/NS/NINDS NIH HHS/United States
GR  - P50 NS2372/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120209
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (DNMT1 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cerebellar Ataxia/*genetics
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/*genetics
MH  - Deafness/*genetics
MH  - Exome
MH  - Exons
MH  - *Genes, Dominant
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Narcolepsy/*genetics
MH  - Pedigree
MH  - Phenotype
PMC - PMC3465691
EDAT- 2012/02/14 06:00
MHDA- 2012/09/14 06:00
PMCR- 2013/05/15
CRDT- 2012/02/14 06:00
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2012/09/14 06:00 [medline]
PHST- 2013/05/15 00:00 [pmc-release]
AID - dds035 [pii]
AID - 10.1093/hmg/dds035 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2012 May 15;21(10):2205-10. doi: 10.1093/hmg/dds035. Epub 2012 Feb 
      9.