Paroxysmal central nervous system disorders
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: 1.3
Publications
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
NarcolepsyCreated: 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
Publications for gene: DNMT1 were set to 23904686; 22328086; 24709307
Gene: dnmt1 has been classified as Green List (High Evidence).
Source NHS GMS was added to DNMT1.
Source London North GLH was added to DNMT1.
Source Wessex and West Midlands GLH was added to DNMT1.
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
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