One dose of an ordinary antibiotic, at an ordinary blood level, and the hearing does not come back. It happens to people carrying one change in mitochondrial DNA — which their mother also has, and so do all of her children.
Aminoglycosides are old, cheap and effective antibiotics. They are also known to damage hearing at high doses or over long courses, which is why blood levels are monitored when they are used.
For some people the monitoring does not help, because the damage does not need a high level. A single standard dose is enough.
Aminoglycosides work by binding the bacterial ribosome and making it read messages wrongly. Mitochondria are descended from bacteria and still carry their own ribosomes, built from their own DNA — which is why they are vulnerable at all.
The m.1555A>G variant changes the mitochondrial ribosomal RNA at exactly the place where the drug binds, making the human mitochondrial ribosome look more like the bacterial one. The drug binds where it should not, and the hair cells of the inner ear — which have a great many mitochondria and are never replaced — are what pays.
Mitochondria come from the egg. So this passes from a mother to every one of her children, and from a father to none of them.
That is unlike anything else on this site, and it has a practical consequence: if one person in a family is found to carry it, the maternal line is the part of the family that needs to know — siblings, mother, mother's siblings, and the children of every woman among them.
Where an alternative antibiotic will work, it is used instead. Where one will not — some severe infections, some resistant organisms, some situations in intensive care — the decision belongs to the treating team weighing a permanent hearing loss against a life-threatening infection. That is a real trade-off and not one to pre-empt from a genotype file.
What the file usefully does is put the information in the record before the emergency, rather than after it.
This variant does not cause hearing loss on its own in most carriers, and it is not a reason to avoid ordinary antibiotics. Aminoglycosides are a specific class — gentamicin, tobramycin, amikacin and their relatives — usually given by injection in hospital. Nothing here applies to the antibiotics most people are handed for a chest infection.
Source. McDermott et al., CPIC Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype (Clin Pharmacol Ther 2022, PMID 34032273).
Mechanism. Aminoglycosides bind the A-site of the bacterial 16S rRNA. The mitochondrial 12S rRNA encoded by MT-RNR1 is homologous; m.1555A>G increases the structural similarity at the binding site, permitting drug binding and impairing mitochondrial translation. Cochlear hair cells are post-mitotic and mitochondria-rich, and the resulting loss is sensorineural and permanent.
Inheritance. Mitochondrial, therefore matrilineal: transmitted by a mother to all offspring and by a father to none. Heteroplasmy — the proportion of mitochondrial genomes carrying the variant — varies, and the relationship between heteroplasmy level and risk is not fully characterised.
Position listed here. rs267606617 (m.1555A>G). Mitochondrial variants are reported as a single allele rather than a genotype pair, because mitochondrial DNA is not inherited in two chromosomal copies. m.1494C>T is a second variant with the same consequence and is not represented on typical consumer arrays.
Clinical use. CPIC recommends avoiding aminoglycosides in carriers unless the infection is life-threatening and no safe or effective alternative exists. Where an aminoglycoside must be used, informed discussion and audiological monitoring are advised. Therapeutic drug monitoring does not protect a carrier, because the toxicity is not dose-dependent in the usual sense.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Aminoglycoside-Induced Hearing Loss comes down to these specific, well-studied positions — not a diagnosis.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| MT-RNR1 | Aminoglycosides (amikacin, gentamicin, tobramycin, kanamycin, streptomycin, neomycin, plazomicin, dibekacin, netilmicin, paromomycin, ribostamycin and related agents) | Avoid in a carrier of m.1555A>G unless the infection is life-threatening and no safe alternative exists. Hearing loss can follow a single standard dose at a therapeutic blood level, so monitoring drug levels does not protect this person — which is the point most easily missed, because level monitoring is the usual safeguard for this class. The guideline covers the whole class rather than only the drugs a hospital reaches for most often: dibekacin, netilmicin, paromomycin and ribostamycin carry the same warning as gentamicin. (CPIC Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype (Clin Pharmacol Ther 2022, PMID 34032273).) |
Very probably, because mitochondria are inherited from the mother and pass to all of her children. The reverse does not hold: if your father carries it, you do not get it from him.
No, and this is the part that surprises clinicians as well as patients. Blood-level monitoring is the standard safeguard for aminoglycosides and it does not help here — the loss can follow one standard dose at a normal level. Avoiding the drug is what protects a carrier.
Not as a rule set in advance. There are infections where an aminoglycoside is the drug that works and the alternative is worse than deafness. That weighing belongs to the treating team, and what helps them is that the information is already in your record.
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