Early onset dementia (encompassing fronto-temporal dementia and prion disease)
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, 4:30 p.m. | Last Modified: 1 Sep 2020, 4:30 p.m.
Panel Version: 1.48
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Comment on list classification: >3 patients with early onset dementia in OMIM and ClinVarCreated: 10 May 2016, 12:57 p.m.
This gene has been classified as Green List (High Evidence).
Publications for DNMT1 were set to 23365052
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
DNMT1 was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease)panel. Sources: Illumina TruGenome Clinical Sequencing Services