Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Hearing Loss, mitochondrial, drug-induced [T88.7]

OMIM numbers: 580000, 561000 (MTRNR1), 516030 (MTCO1)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh, Dipl.-Biol. Birgit Busse

Scientific Background

Irreversible hearing loss is a severe complication of treatment with aminoglycoside antibiotics such as streptomycin, gentamicin and kanamycin. It has been known for many years that mutations in the maternally inherited mitochondrial genes play an important role. A mutation in the position mt.1494C>T and mt.1555A>G of the mitochondrial 12S rRNA gene (MTRNR1) is associated with the risk of aminoglycoside-induced deafness. The mechanism of action of the aminoglycosides is due to the irreversible binding to the 30S subunit of the bacterial ribosomes that leads to a dysfunction in the protein biosynthesis.

Mutations of the mitochondrial cytochrome C oxidase subunit I (MTCO1 gene) in the position mt.7444G>A and mt.7445A>G have also been associated with an increased risk for aminoglycoside induced deafness, as well as with nonsyndromic, sensorineural hearing loss. A combined carrier status of the mutations mt.1555A>G and mt.7444G>A seems to pose the highest risk for hearing loss. Moreover, rare mutations in the mitochondrial tRNASer(UCN) gene were identified in association with aminoglycoside-induced hearing loss.