Description
The variant MT-RNR1:n.908A>G, m.1555A>G is located in the 12S rRNA gene (MT-RNR1) and results from an adenine to guanine at nucleotide position 1555. It has been described in numerous cases with mitochondrial non-syndromic hearing loss (PMID: 7689389, 1613771, 8285309, 8414970, 9111378, 9040738, 9490575, 9831149, 10661905, 12031626, 12920080, 16935512, 20123042, 22317974, 23357420, 24252789, 11870684). Although the variant is present at homoplasmy in unaffected individuals, multiple individuals harboring the variant were reported to have hearing loss after amynoglycoside exposure. Non amynoglycoside exposure-related loss hering have been also reported. Age of onset of hearing loss ranged from infancy (after aminoglycoside exposure) to adulthood. Overall, aminoglycoside-based antibiotic treatments are known to increase the risk of hearing loss in carriers of this alteration (PMID: 29805548, 25515069). Multiple studies provide experimental evidences supporting a deleterious functional effect of the variant (PMID: 11230176, 8817331, 8687424). The variant is not considered rare in the overall population (MAF 0.1% for homoplasmy in gnomAD V3.1). The ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel suggest to classify of Pathogenic (Clinvar: 9628). Based on available evidence, the variant is classified as Likely Pathogenic.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | 1 | not provided | not provided | not provided |