Hereditary ataxia
Gene: DNMT1EnsemblGeneIds (GRCh38): ENSG00000130816
EnsemblGeneIds (GRCh37): ENSG00000130816
OMIM: 126375, Gene2Phenotype
DNMT1 is in 13 panels
3 reviews
Eleanor Williams (Genomics England Curator)
Additional functional evidence: PMID: 31984424 - Maresca et al - studied the effects of different DNMT1 mutations in fibroblasts from four Autosomal Dominant Cerebellar Ataxia-Deafness and Narcolepsy (ADCA-DN) and two Hereditary Sensory Neuropathy with Dementia and Hearing loss (HSN-IE) patients who were unrelated. They found mitochondrial hyper-function that resulted in increased oxidative stress but no change in mitochondrial DNA CpG methylation. They demonstrated that DNMT1 is not localized within mitochondria, but it is associated to the mitochondrial outer membrane. AMPK and mTORC1, the two major sensors of cellular energy, were implicated in the pathogenic mechanism of the most severe DNMT1 mutations.Created: 1 Sep 2020, 4:32 p.m. | Last Modified: 1 Sep 2020, 4:32 p.m.
Panel Version: 1.205
Publications
Damian Smedley (Genomics England Curator)
Comment on list classification: Evidence from expert reviewer and OMIMCreated: 4 Feb 2016, 2:03 p.m.
Jonathan Williams (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust)
Fine lots of evidence in lit. Mode of inheritance/pathogenicity: Dominant negative?Created: 24 Nov 2015, 4:57 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant,
Mode of pathogenicity
Other - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- UKGTN
- Radboud University Medical Center, Nijmegen
- Phenotypes
-
- Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant,
- OMIM
- 126375
- Clinvar variants
- Variants in DNMT1
- Penetrance
- Complete
- Panels with this gene
-
- Monogenic hearing loss
- Hereditary ataxia
- Paroxysmal central nervous system disorders
- Adult onset neurodegenerative disorder
- Intellectual disability
- Childhood onset dystonia, chorea or related movement disorder
- Hereditary ataxia with onset in adulthood
- Early onset dementia (encompassing fronto-temporal dementia and prion disease)
- Familial dysautonomia
- Kleine-Levin syndrome
- Hereditary neuropathy
- Hereditary neuropathy or pain disorder
- Ataxia and cerebellar anomalies - narrow panel
History Filter Activity
Gene classified by Genomics England curator
Damian Smedley (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set Mode of Inheritance
Damian Smedley (Genomics England Curator)Mode of inheritance for DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene classified by Genomics England curator
Damian Smedley (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set Mode of Inheritance
Ellen McDonagh (Genomics England Curator)Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added New Source
Ellen McDonagh (Genomics England Curator)DNMT1 was added to Hereditary ataxiapanel. Sources: Radboud University Medical Center, Nijmegen,UKGTN
Added New Source
Ellen McDonagh (Genomics England Curator)DNMT1 was added to Hereditary ataxiapanel. Sources: Radboud University Medical Center, Nijmegen,UKGTN