Table 4.
Descriptive features of selected studies which investigated DNMT1 mutations in humans with relation to hearing loss
| Human DNMT1 mutation studies | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Author/Year | Country | Disease | Design | Covariates | Sample Size | Sex/Age | Main Objective | Results | Rep |
| Davis K. N. 2023 [18] | Italy & Sweden | ADCA-DN | Ips and Ins cells derived from patient and control fibroblasts examined via genome-wide target capture sequencing, pyrosequencing and RNA-seq | NA |
n = 6 case = 3 ctrl = 3 |
M Only/ 32–57 |
ips and ins cells derived from ADCA-DN patients were assessed for DNA methylation and gene expression changes | Functional DNMT1 mutations in ADCA-DN induce global, and cell type-specific, changes to patterns of DNA methylation and gene expression | No |
| Ding E et al. 2018 [19] | China | NA | SNP selection from Genotyping | Smoking & Alcohol | n = 1054 case = 527 ctrl = 527 | Explore effects of DNMT1 and DNMT3A polymorphisms on susceptibility to NIHL in Chinese workers | Haplotypes AGGG and TGGA (rs7578578-rs749131-rs1550117-rs2228611) & GG genotype at rs749131 and the AG/GG genotypes at rs1550117 and rs2228611 associated with higher risk of NIHL | No | |
| Klein C.J. 2011 [20] | Europe | HSAN1 with dementia and SNHL | Exome Sequencing | NA | n = 63 | Show mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of HSAN1 with dementia and hearing loss | Mutation c.A1484G (p.Tyr495Cys) and triple nucleotide change c.1470TCC-1472ATA (p.Asp490Glu-Pro491Tyr) within targeting sequence of DNMT1 in HSAN1) with dementia and hearing loss patients | No | |
| Menon P.J. 2023 [21] | Ireland | Progressive deafness, mild cognitive decline and apathy | WES | NA |
n = 1 case = 1 |
M/ 42 |
Examination of clinical patient | Novel variant found overlapping HSN1E-cerebellar phenotype | No |
| Moghadam KK et al. 2014 [22] | Italy | NA | Genetic Tests | ADCA-DN parent |
n = 2 case = 2 |
F/ 23–28 |
Report the clinical picture of two asymptomatic daughters of a patient with ADCA-DN due to DNMT1 mutation | Mutation on exon 21 of the DNMT1 gene–p.Ala570Val (RefSeq NM_001130823.1: c.1709G.A) | No |
| Winkelmann J et al., 2012 [23] | Italy, USA & Sweden | ADCA-DN | WES | NA |
n = 5 case = 5 |
No info/ 29–47 |
To identify the cause of ADCA-DN | Mutations located in exon 21 of DNMT1 and in very close spatial proximity, suggesting distinct phenotypes depending on mutation location within this gene | No |
| Zheng W et al. 2018 [24] | China | Sporadic cerebellar ataxia, multiple motor and sensory neuropathy, hearing loss and psychiatric manifestations | WES | NA | n = 1 |
F/ 38 |
Report a Chinese patient with suspected HSAN1E, confirmed by exome sequencing | Novel heterozygous missense variant, c 1618 T > A (p. Y540N) in exon 20 of the DNMT1, which is associated with HSAN1E | No |
| Kernohan, K. D., et al. 2016 [25] | Canada, Ontario | ADCA-DN | Familial segregation study. 450 K Methylation Array | NA | n = 6 | Describe a family with ADCA-DN caused by mutations in DNMT1 and assess the DNA methylation profile of these individuals | A heterozygous DNMT1 variant, c.1709C > T [p.Ala570Val] by Sanger sequencing pathogenic for ADCA-DN segregated with disease in the family. Eighty-two significantly hypermethylated regions with further work required to understand significance of these regions to the disease | No | |
ADCA-DN Autosomal dominant cerebellar ataxia, deafness, and narcolepsy, Ips Induced Pluripotent Cells, Ins Induced Neuronal Cells,HSAN1 hereditary sensory and autonomic neuropathy, SNHL Sensory Neuronal Hearing Loss, NIHL noise-induced hearing loss, WES whole exome sequencing