Kleine-Levin syndrome
Gene: DNMT1EnsemblGeneIds (GRCh38): ENSG00000130816
EnsemblGeneIds (GRCh37): ENSG00000130816
OMIM: 126375, Gene2Phenotype
DNMT1 is in 13 panels
2 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, 4:29 p.m. | Last Modified: 1 Sep 2020, 4:29 p.m.
Panel Version: 1.4
Publications
Sarah Leigh (Genomics England Curator)
Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. At least 9 variants reportedCreated: 5 Jan 2017, 9:39 a.m.
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Green
- Illumina TruGenome Clinical Sequencing Services
- Emory Genetics Laboratory
- UKGTN
- Radboud University Medical Center, Nijmegen
- Phenotypes
-
- Neuropathy, hereditary sensory, type IE, 614116
- Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121
- CEREBELLAR ATAXIA, DEAFNESS, AND NARCOLEPSY, AUTOSOMAL DOMINANT
- ADCADN
- OMIM
- 126375
- Clinvar variants
- Variants in DNMT1
- Penetrance
- Complete
- Publications
- Panels with this gene
-
- Monogenic hearing loss
- Hereditary ataxia
- Paroxysmal central nervous system disorders
- Hereditary neuropathy or pain disorder
- Adult onset neurodegenerative disorder
- 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
- Ataxia and cerebellar anomalies - narrow panel
- Intellectual disability
History Filter Activity
Set publications
Eleanor Williams (Genomics England Curator)Publications for gene: DNMT1 were set to 22328086; 24709307; 23904686
panel promoted to version 1
Sarah Leigh (Genomics England Curator)Rosa Peraita-Adrados (Sleep and Epilepsy Unit-Clinical Neurophysiology Service. Gregorio Maranon University Hospital. Complutense University of Madrid (UCM).Madrid.Spain.), agrees with the status of the gene on this panel, although she has not reviewed every gene individually
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set publications
Sarah Leigh (Genomics England Curator)Publications for DNMT1 were set to 22328086; 24709307; 23904686
Upload gene information
Sarah Leigh (Genomics England Curator)DNMT1 was added to Kleine-Levin syndromepanel. Sources: Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory
Set publications
Sarah Leigh (Genomics England Curator)Publications for DNMT1 were set to 22328086
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 Kleine-Levin Syndrome (KLS) and other inherited sleep disorders panel. Sources: UKGTN
Added New Source
Ellen McDonagh (Genomics England Curator)DNMT1 was added to Kleine-Levin Syndrome (KLS) and other inherited sleep disorders panel. Sources: Radboud University Medical Center, Nijmegen