Monogenic hearing loss
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, 4:34 p.m. | Last Modified: 1 Sep 2020, 4:34 p.m.
Panel Version: 2.44
Publications
Comment on mode of inheritance: Imprinted gene list checked.Created: 17 Feb 2016, 2:24 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
#604121:Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant[Sensorineural deafness; Optic atrophy (in some patients); Limb lymphedema (in some patients); NarcolepsyExcessive daytime sleepinessREM sleep behavior disorderCerebellar ataxiaSpasticityHyperreflexiaMemory lossDementiaPrimitive reflexesCerebellar atrophy; Sensorimotor polyneuropathy; Depression (in some patients)Psychosis (in some patients); Decreased CSF hypocretin]; #614116:Neuropathy, hereditary sensory, type IE[Hearing loss, sensorineural; Ulceration of the toesOsteomyelitisAmputation; Memory impairment, progressiveDementia, frontal lobeDecreased speechCerebral atrophyFrontal lobe atrophyHypometabolism of the frontal lobe and thalamic regions; Sensory neuropathy affecting all modalities primarily affecting the lower limbs with some mild upper limb involvementHyporeflexiaLancinating pains (2 patients)Almost complete loss of myelinated fibers seen on sural nerve biopsyLoss of unmyelinated fibers; ApathySomnolenceImpulsivityIrritabilityDistractibilityDelirium]
Publications
Comment when marking as ready: Expert review and OMIM confirmedCreated: 29 Jan 2016, 3:17 p.m.
Publications for gene: DNMT1 were set to PMID:10325416; 10433969; 10449766; 10545955; 10615135; 10721735; 10753866; 10801130; 10888872; 10888886; 11005794; 11074872; 11290321; 11728338; 11884600; 11932749; 11940649; 12145218; 12473678; 12496760; 12702876; 12915469; 14615517; 14684836; 14749379; 14978102; 15215866; 15311210; 1559980; 15657147; 15684088; 15870198; 1594447; 1606615; 16357870; 16998846; 17312023; 17322882; 17359920; 17470536; 17673620; 17960246; 17994007; 18194272; 19098913; 19246518; 19433415; 1968655; 20081831; 2014266; 21163962; 21532572; 22323818; 22328086; 23365052; 24013172; 24107992; 3210246; 7898717; 8747854; 8917520; 8940105; 9302295; 9333948; 9449671
Publications for DNMT1 were set to PMID:10325416; 10433969; 10449766; 10545955; 10615135; 10721735; 10753866; 10801130; 10888872; 10888886; 11005794; 11074872; 11290321; 11728338; 11884600; 11932749; 11940649; 12145218; 12473678; 12496760; 12702876; 12915469; 14615517; 14684836; 14749379; 14978102; 15215866; 15311210; 1559980; 15657147; 15684088; 15870198; 1594447; 1606615; 16357870; 16998846; 17312023; 17322882; 17359920; 17470536; 17673620; 17960246; 17994007; 18194272; 19098913; 19246518; 19433415; 1968655; 20081831; 2014266; 21163962; 21532572; 22323818; 22328086; 23365052; 24013172; 24107992; 3210246; 7898717; 8747854; 8917520; 8940105; 9302295; 9333948; 9449671
Mode of inheritance for DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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 Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Model of inheritance for gene DNMT1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DNMT1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
DNMT1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen