Mitochondrial mutations in maternally inherited hearing loss

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Mitochondrial DNA (mtDNA) mutations, particularly m.1555A>G and m.3243A>G, are established causes of maternally inherited sensorineural hearing loss (SNHL).
• However, other mtDNA mutations are also implicated in SNHL, necessitating broader screening approaches.

Purpose of the Study:

• To establish clinical criteria for identifying individuals with SNHL who are likely to have underlying mtDNA mutations.
• To investigate the spectrum of mtDNA mutations associated with SNHL beyond the common variants.

Main Methods:

• Screening of 145 probands for known mtDNA mutations (m.1555A>G and m.3243A>G).
• Application of five specific clinical criteria to identify high-risk probands for further investigation.
• Sequencing of additional mtDNA regions in selected subjects meeting the clinical criteria.

Main Results:

• Nine probands met the stringent clinical criteria for suspected mtDNA-related SNHL.
• Among these, three had the m.1555A>G mutation, one had the m.3243A>G mutation, and one presented with a novel m.7511T>C mutation in MTTS1.
• The m.7511T>C mutation showed variable penetrance (53%) and age of onset, with no distinct clinical characteristics.

Conclusions:

• The developed clinical criteria are effective in identifying candidate patients with SNHL likely caused by mtDNA mutations.
• The findings highlight the importance of considering a wider range of mtDNA mutations in the genetic diagnosis of SNHL.