Several members of a family develop irreversible sensorineural deafness after a single course of streptomycin given for tuberculosis. Screening would most likely reveal a pathogenic variant in which gene?

• A Mitochondrial cytochrome b gene
• B Nuclear GJB2 connexin gene
• C Mitochondrial 12S ribosomal RNA gene ✓
• D Nuclear SOD1 gene

Explanation

Maternally inherited susceptibility to aminoglycoside ototoxicity maps to homoplasmic mutations in the mitochondrial 12S rRNA gene, most famously the C1555G transition. The mutant ribosome structurally resembles bacterial 16S rRNA, allowing aminoglycoside binding and hair cell death, so a single exposure can cause profound permanent deafness. Connexin 26 mutations cause nonsyndromic congenital deafness but do not confer aminoglycoside susceptibility.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.