Frequent mutations associated with hearing loss: m.1555A>G, m.1494C>T, m.1095T>C, m.961delInsC, m.961T>C, m.7445A>G y m.7445A>C

Deafness of mitochondrial origin is related in nearly 100% of cases to variants in 3 positions of the mitochondrial genome, specifically in the MT-RNR1 genes (m.1555A>G and m.1494C>T) and in MT-TS1 ( m.7445A>C/T/G).

Pathogenic variants in MT-RNR1 are associated with both predisposition to aminoglycoside ototoxicity and late-onset non-syndromic sensorineural deafness. However, pathogenic variants in MT-TS1 are often associated with the onset of deafness in childhood. The latter is also generally nonsyndromic, although the MT-TS1 m.7445A>G substitution has been found in some families that also have palmoplantar keratoderma.

  • MT-RNR1 m.1555A>G variant: 0.19% of newborns in Europe (NBK1422).
  • MT-RNR1 m.1494C>T variant: 0.07% in the USA (NBK1422).

It is advisable to request a genetic study for sensorineural deafness, as long as there are no clinical data compatible with a non-genetic etiology. If family deafness is evident with a pattern highly suggestive of mitochondrial inheritance, it would be indicated to start with this service, as it solves close to 100% of cases of mitochondrial deafness. The benefits derived from a genetic study in this context are especially aimed at completing the diagnosis and family genetic counseling.

Service is indicated when sensorineural deafness is diagnosed and a mitochondrial genetic origin is suspected in the absence of other causal agents and a compatible family history.

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Frequent mutations associated with hearing loss: m.1555A>G, m.1494C>T, m.1095T>C, m.961delInsC, m.961T>C, m.7445A>G y m.7445A>C

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Technique: Fragment Analysis

Turnaround time (TAT): 25 days

Ref. S-202212831

Frequent mutations associated with hearing loss: m.1555A>G, m.1494C>T, m.1095T>C, m.961delInsC, m.961T>C, m.7445A>G y m.7445A>C: View panel

Sequencing with high reading depth in the positions of the mitochondrial genome where practically all variants related to this phenotype and mode of transmission occur. If a very high clinical suspicion persists after a non-informative result, it is advisable to expand to a complete mitochondrial genome, where other causes can be sought.

  • m.1555A>G
  • m.1494C>T
  • m.1095T>C
  • m.961delInsC
  • m.961T>C
  • m.7445A>G
  • m.7445A>C

Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.

Phenotypes

Hearing loss of mitochondrial origin

References

  1. Usami S, Nishio S. Nonsyndromic Hearing Loss and Deafness, Mitochondrial. 2004 Oct 22 [Updated 2018 Jun 14]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1422/