MATERNALLY INHERITED SENSORINEURAL HEARING LOSS (MISNHL)

Seven Mutations

MITOCHONDRIAL DNA ANALYSIS

The proportion of hearing loss caused by mutations in mitochondrial DNA is not known. However, syndromic hearing loss appears to be one of the most prevalent clinical features associated with mitochondrial diseases caused by a variety of mtDNA mutations. The most common mtDNA mutations responsible for non-syndromic maternally inherited sensorineural hearing loss localize to two regions of the mitochondrial genome: the 12S rRNA and the tRNA ser(UCN) genes. The most common mtDNA mutation shown to cause nonsyndromic hearing loss in humans is the 1555A>G mutation in the small ribosomal RNA gene (12S rRNA) of the mitochondrial genome. This mutation causes hypersensitivity to the ototoxic effects of aminoglycosides. The other hot spot for non-syndromic MISNHL is the tRNA ser(UCN) gene. For mitochondrial syndromic hearing loss, Mitochondrial DNA Screen (Point Mutations and Deletions) should be ordered.

Reasons for Referral:

To confirm the diagnosis of non-syndromic maternally inherited hearing loss.
Family history

Testing Methodology:

Portion of the 12S rRNA gene and the entire tRNA ser(UCN) gene of the mitochondrial genome are PCR amplified and sequenced. The mutations particularly responsible for non-syndromic maternally inherited hearing loss; 1494C>T, 1555A>G, 7510T>C, 7511T>C, 7512T>C, 7472 insC, and 7445A>G, are analyzed.

Sensitivity:

In general, sequence analysis does not detect low mutant heteroplasmy. Sometimes heteroplasmy <50% may not be detected.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc
Tissue: Skeletal muscle (Preferred). 50 mg for muscle DNA analysis, 150mg for muscle ETC analysis, >200mg if additional tests are requested. Heart, brain, liver, kidney or fibroblast cultures also accepted. 50 mg of heart, brain, liver, kidney or fibroblast for DNA analysis. Tissues such as liver and kidney should be snap-frozen at collection, stored at -70, and shipped on 3-5 lbs of dry ice.

Turnaround Time:

3 weeks

CPT Codes and Prices:

Index: 83904x4, 83912, 83898x4, 83891
Known Familial Mutation: 83912, 83900, 83901x2, 83904x2, 83894x2, 83891

Shipping Information

Forms:

>> Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included

References:

Hsu CH, Kwon H, Perng CL, Bai RK, Dai P, Wong LJ. (2005) Hearing loss in mitochondrial disorders. Ann. N Y Acad. Sci. 1042: 36-47.
Zhao H, Li R, Wang Q, Yan Q, Deng JH, Han D, Bai Y, Young WY, Guan MX. (2004) Maternally inherited aminoglycoside-induced and non-syndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family. Am. J. Hum. Genet. 74: 139-152.

Test Codes:

Index: 3030
Known Familial Mutation: 3031