MT-RNR1 genotyping to identify risk of aminoglycoside-induced ototoxicity (Test code R65.1)
Approximately 1 in 500 people have a mitochondrial variant in the MT-RNR1 gene predisposing them to ototoxicity (hearing loss and vestibular disorders) with aminoglycoside antibiotics.
Testing is currently available for patients at high risk of gram-negative infection due to an underlying medical condition, or those with hearing loss after exposure to aminoglycosides. This involves targeted genomic testing of the MT-RNR1 m.1555A>G, m.1095T>C and m.1494C>T variants. The level of the MT-RNR1 mitochondrial variant (heteroplasmy) may vary between tissues. Therefore, this assay does not exclude the presence of a low level variant or a variant outside of the region tested. Hearing loss following the use of aminoglycosides, as a result of drug toxicity due to other clinical factors, including other non-genetic causes of aminoglycoside induced ototoxicity, cannot be excluded.
As testing may take up to weeks, it is only appropriate to be used pre-emptively, rather than at the point of antibiotic prescribing.
More information
Test Eligibility
Please see R65 Aminoglycoside exposure posing risk to hearing (www.england.nhs.uk/publication/national-genomic-test-directories/) for testing criteria.
Test order form
Testing should be ordered using the standard SW GMS test order form:
This should be completed in full & include the test indication ‘MT-RNR1 genotyping for patient predisposed to gram-negative infection due to an underlying medical condition’ OR ‘MT-RNR1 genotyping for patient with hearing loss following exposure to aminoglycosides’
Alternatively, local test request forms with the equivalent information are acceptable.
Genotyping for MT-RNR1 will be undertaken as a reflex test following confirmed Cystic Fibrosis genotyping (test codes R184 or R253) using the same EDTA blood sample. In this instance a test request form is not required.
Samples and transport
- Please ensure that the patient identity has been verified before taking the sample.
• The sample should be labelled with at least 3 patient identifiers including the patient’s name and date of birth.
• Please send the completed referral form and the labelled patient sample (1-2ml for neonates, 2-5ml for adults of EDTA blood) to the nearest designated Genomics Laboratory, via the local pathology laboratory:
Bristol Genetics Laboratory
Southmead Hospital
Westbury-on-Trym
Bristol
BS10 5NB
Exeter Genomics Laboratory
Level 3 RILD building
Royal Devon & Exeter NHS Foundation Trust
Barrack Road
Exeter
EX2 5DW
Transportation instructions
- Samples should be sent at room temperature. If there is a delay in sending, the sample can be refrigerated at +4oC (do not freeze) and should be received by the genomics laboratory within 5 days of venesection.
- The sample container should be leak-proof and must be placed in a transparent sample bag with the paperwork attached but not in the same compartment as the container. The outer sample packaging must comply with PI 650 for category B substances. The package should be clearly labelled ‘diagnostic specimen UN3373’.
- Samples should be sent to the laboratory via your local hospital transport services or directly using first class via the Royal Mail postal services.
For full instructions, please visit the sample requirements and transport information page
Test methodology
Sanger sequence analysis of the m.1095, m.1494 and m.1555 nucleotides of the MT-RNR1 (12S rRNA) gene.
Results and turnaround times
- Reports will be returned by email within 6 weeks as a pdf-document.
- Report recipient details (name, job title and email address) should be specified on the referral form.
For more information please visit the results and turnaround times section.
Further information
Patient information for mtRNR1 genotyping for Cystic Fibrosis patients MT-RNR1 Testing.pdf