Hereditary ataxia
Gene: DNMT1Additional 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
Comment on list classification: Evidence from expert reviewer and OMIMCreated: 4 Feb 2016, 2:03 p.m.
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
This gene has been classified as Green List (High Evidence).
Mode of inheritance for DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DNMT1 was added to Hereditary ataxiapanel. Sources: Radboud University Medical Center, Nijmegen,UKGTN
DNMT1 was added to Hereditary ataxiapanel. Sources: Radboud University Medical Center, Nijmegen,UKGTN