Hereditary neuropathy
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, 4:33 p.m. | Last Modified: 1 Sep 2020, 4:33 p.m.
Panel Version: 1.375
Publications
PMID: 21532572 - identified 2 different heterozygous mutations in 4 unrelated familiesCreated: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Neuropathy, hereditary sensory, type IE, 614116; other; Neuropathy, hereditary sensory, type IE, 614116 ; Dementia, Deafness, and Sensory Neuropathy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.Created: 9 May 2019, 5 p.m.
Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 29 Apr 2019, 12:53 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: DNMT1 were set to 21532572
Phenotypes for gene: DNMT1 were changed from Neuropathy, hereditary sensory, type IE, 614116; other; Neuropathy, hereditary sensory, type IE, 614116; Dementia, Deafness, and Sensory Neuropathy to Neuropathy, hereditary sensory, type IE, 614116; Neuropathy, hereditary sensory, type IE, 614116; Dementia, Deafness, and Sensory Neuropathy
Phenotypes for gene: DNMT1 were changed from other; Dementia, Deafness, and Sensory Neuropathy; Neuropathy, hereditary sensory, type IE, 614116; other; Dementia, Deafness, and Sensory Neuropathy ; Neuropathy, hereditary sensory, type IE, 614116 to Neuropathy, hereditary sensory, type IE, 614116; other; Neuropathy, hereditary sensory, type IE, 614116; Dementia, Deafness, and Sensory Neuropathy
Added phenotypes Dementia, Deafness, and Sensory Neuropathy; other; Neuropathy, hereditary sensory, type IE, 614116 for gene: DNMT1 Publications for gene DNMT1 were changed from to 21532572
Source South West GLH was added to DNMT1.
Source NHS GMS was added to DNMT1.
Source London North GLH was added to DNMT1. Rating Changed from Green List (high evidence) to Green List (high evidence)
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
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DNMT1 was added to Charcot-Marie-Tooth diseasepanel. Sources: Expert list,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DNMT1 was added to Charcot-Marie-Tooth diseasepanel. Sources: Expert list,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DNMT1 was added to Charcot-Marie-Tooth diseasepanel. Sources: Expert list,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory
DNMT1 was added to Charcot-Marie-Tooth diseasepanel. Sources: Expert list,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory