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HelpMayo Test ID AIHL Aminoglycoside-Induced Hearing Loss, Targeted Variant Testing, Droplet Digital PCR, Varies
Ordering Guidance
The preferred genetic test for diagnosis in individuals with suspicion of syndromic or non-syndromic hereditary hearing loss is HHLP / AudioloGene Hereditary Hearing Loss Panel, Varies.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient/Refrigerated/Frozen
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Collection Kit (T786)
Specimen Volume: 1 swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient
Useful For
Identification of individuals who may be at risk for aminoglycoside-induced hearing loss (AIHL)
Establishing a diagnosis of late-onset sensorineural hearing loss associated with aminoglycoside exposure
Identifying mitochondrial variants associated with AIHL, allowing for predictive testing of at-risk family members
Special Instructions
Method Name
Droplet Digital Polymerase Chain Reaction (ddPCR)
Reporting Name
Aminoglycoside-Induced Hearing LossSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Aminoglycosides (tobramycin, streptomycin, and gentamicin, etc) are a group of broad-spectrum antibiotics commonly prescribed for infections caused by Gram-negative bacteria. In the United States alone, approximately 4 million courses of aminoglycosides are administered each year with approximately 2% to 5% of patients treated developing clinically significant hearing loss. Mitochondrial gene RNR1 (MT-RNR1) variants m.1555A>G and m.1494C>T are the most common variants associated with aminoglycoside-induced ototoxicity. Hearing loss associated with aminoglycoside exposure can occur even after a single dose and may be bilateral, irreversible, and often severe to profound. Avoidance of aminoglycoside antibiotics reduces the risk of developing hearing loss for individuals carrying one of these 2 variants.
The severity and onset of hearing loss in individuals with the associated pathogenic mitochondrial variants range from profound congenital deafness to mild to moderate late-onset hearing loss. Evidence demonstrates that this variance can often be explained by variant load in an individual. In contrast to variants in nuclear genes, which are present in either 0, 1, or 2 copies, mitochondrial variants can be present in any fraction of the total organelles, a phenomenon known as heteroplasmy. Penetrance of hearing loss without exposure to aminoglycosides is thought to be a function of the degree of heteroplasmy, with a correlation between higher fraction of altered mitochondria and higher penetrance. Hearing loss is believed to be 100% penetrant in homoplasmic individuals who receive aminoglycoside antibiotics.
Reference Values
An interpretive report will be provided.
Interpretation
An interpretive report will be provided.
Cautions
Clinical Correlations:
Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.
Technical Limitations:
This assay will not detect all variants or genes that cause mitochondrial nonsyndromic hearing loss and deafness. Therefore, the absence of a detectable variant does not rule out the possibility that an individual is a carrier of or affected with mitochondrial non-syndromic hearing loss and deafness.
Some individuals who are a carrier or have a diagnosis of mitochondrial nonsyndromic hearing loss and deafness may have a variant that is not identified by this assay. The absence of a variant, therefore, does not eliminate the possibility of a hereditary hearing loss disorder. For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene variant in an affected family member.
Of note, absence of the mitochondrial variants MT-RNR1 m.1494C>T or MT-RNR1 m.1555A>G does not rule out the presence of these variants below the limits of detection of this assay (<5% heteroplasmy).
Rare alterations exist that could lead to false-negative or false-positive results. If results obtained do not match clinical findings, additional testing should be considered.
Clinical Reference
1. Gao Z, Chen Y, Guan MX: Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity. J Otol. 2017 Mar;12(1):1-8
2. Krause KM, Serio AW, Kane TR, Connolly LE: Aminoglycosides: An overview. Cold Spring Harb Perspect Med. 2016 Jun 1;6(6):a027029
3. Qian Y, Guan MX: Interaction of aminoglycosides with human mitochondrial 12S rRNA carrying the deafness-associated mutation. Antimicrob Agents Chemother. 2009 Nov;53(11):4612-4618
4. Usami S, Nishio S: Nonsyndromic hearing loss and deafness, mitochondrial. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2004. Updated June 14, 2018. Accessed March 15, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1422/
Method Description
This test is a droplet digital polymerase chain reaction method for the detection of MT-RNR1 m.1494C>T and MT-RNR1 m.1555A>G associated with aminoglycoside-induced hearing loss. Variant nomenclature is based on the following GenBank Accession number (build GRCh37 [hg19]): NC_012920.1.(Unpublished Mayo method)
Day(s) Performed
Monday through Saturday
Report Available
1 to 7 days-Specimens must arrive in the performing laboratory by 12 p.m. for the report to be available 1 day from specimen receipt.Specimen Retention Time
Whole Blood: 2 weeks (if available); Extracted DNA: IndefinitelyPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81401
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| AIHL | Aminoglycoside-Induced Hearing Loss | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 609786 | Specimen | 31208-2 |
| 609787 | Source | 31208-2 |
| 609788 | Result Summary | 50397-9 |
| 609789 | Result | 82939-0 |
| 609790 | Interpretation | 69047-9 |
| 609791 | Additional Information | 48767-8 |
| 609792 | Method | 85069-3 |
| 609793 | Disclaimer | 62364-5 |
| 609794 | Released By | 18771-6 |