Paroxysmal central nervous system disorders

Gene: DNMT1

Green List (high evidence)

DNMT1 (DNA methyltransferase 1)
EnsemblGeneIds (GRCh38): ENSG00000130816
EnsemblGeneIds (GRCh37): ENSG00000130816
OMIM: 126375, Gene2Phenotype
DNMT1 is in 15 panels

4 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: 1.3

Publications

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) was collated (February 2019) on behalf of London North GLH for the GMS Neurology specialist test group.
Created: 2 Sep 2019, 2:39 p.m. | Last Modified: 2 Sep 2019, 2:39 p.m.
Panel Version: 0.26
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust) was collated (February 2019) on behalf of West Midlands, Oxford and Wessex GLH for the GMS Neurology specialist test group.
Created: 2 Sep 2019, 1:39 p.m. | Last Modified: 2 Sep 2019, 1:39 p.m.
Panel Version: 0.23

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Narcolepsy
Created: 2 Sep 2019, 1:30 p.m. | Last Modified: 2 Sep 2019, 1:30 p.m.
Panel Version: 0.22

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116

Variants in this GENE are reported as part of current diagnostic practice

History Filter Activity

1 Sep 2020, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: DNMT1 were set to 23904686; 22328086; 24709307

24 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: dnmt1 has been classified as Green List (High Evidence).

2 Sep 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to DNMT1.

2 Sep 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source London North GLH was added to DNMT1.

2 Sep 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to DNMT1.

3 Jan 2019, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Added phenotypes Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116; CEREBELLAR ATAXIA, DEAFNESS, AND NARCOLEPSY, AUTOSOMAL DOMINANT; ADCADN for gene: DNMT1

3 Jan 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: DNMT1 was added gene: DNMT1 was added to Paroxysmal neurological disorders, pain disorders and sleep disorders. Sources: Expert Review Green Mode of inheritance for gene: DNMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DNMT1 were set to 23904686; 22328086; 24709307 Phenotypes for gene: DNMT1 were set to Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116; CEREBELLAR ATAXIA, DEAFNESS, AND NARCOLEPSY, AUTOSOMAL DOMINANT; ADCADN