Hereditary ataxia

Gene: DNMT1

Green List (high evidence)

DNMT1 (DNA methyltransferase 1)
EnsemblGeneIds (GRCh38): ENSG00000130816
EnsemblGeneIds (GRCh37): ENSG00000130816
OMIM: 126375, Gene2Phenotype
DNMT1 is in 15 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 OMIM
Created: 4 Feb 2016, 2:03 p.m.

Jonathan Williams (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust)

Green List (high evidence)

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

History Filter Activity

4 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Damian Smedley (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

4 Feb 2016, Gel status: 4

Set Mode of Inheritance

Damian Smedley (Genomics England Curator)

Mode of inheritance for DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

4 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Damian Smedley (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

6 Jul 2015, Gel status: 2

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

6 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

DNMT1 was added to Hereditary ataxiapanel. Sources: Radboud University Medical Center, Nijmegen,UKGTN

6 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DNMT1 was added to Hereditary ataxiapanel. Sources: Radboud University Medical Center, Nijmegen,UKGTN