Mitochondrial 12S rRNA mutations in Deafness Families from Southern China

HUANG Lusha; CEN Xiaoqing; LIANG Yue; WANG Yueying; WANG Juan; FANG Shubin; JIANG Hongyan; CHEN Kaitian

doi:10.3969/j.issn.1672-2922.2025.03.015

Abstract：Objective To report mutational spectrum characteristics of the mitochondrial 12S rRNA gene in deafness patients from South China,to identify potential candidate mutation sites.Methods Patients with sporadic or familial hearing impairment from southern China areas including Guangdong,Guangxi,Hainan,Fujian and Jiangxi seen at the First Affiliated Hospital of Sun Yat-Sen University from May 2010 to November 2020(n=312),as well as age-matched individuals with normal hearing from the same period(n=180),were included.Medical history and clinical phenotypes analysis were collected from the patients with non-syndromic deafness or drug-induced deafness.Mitochondrial 12S rRNA mutations were detected by Sanger sequencing.Pyrosequencing was conducted to detect TRMU gene m.7445A>G,m.7444G>A mutation and mutation thresholds.Functional analyses for putative pathogenic mitochondrial mutations were completed including structural and phylogenetic analyses.Results Mitochondrial 12S rRNA tests revealed 28 variants,including five known and putative pathogenic mutations,i.e.m.827A>G,m.961insC,m.1005T>C,m.1027A>G and m.1555A>G,and one novel substitutions m.1236C>T mutation.The rate of probable pathogenic mutations was 5.77%(18/312).No TRMU m.7445A>G or m.7444G>A mutation was found.The effect of mitochondrial mutation threshold on phenotypic modification was unclear.Mitochondrial structural analysis and phylogenetic analysis indicated that m.1555A>G,m.827A>G and m.1005T>C were pathogenic in drug-induced deafness,and association of m.1027A>G,m.961insC and newly discovered m.1236C>T with deafness.The pathogenicity of m.750A>G and m.1438A>G remains to be studied.Conclusion The rate of mitochondrial 12S rRNA mutations is increased in non-syndromic and aminoglycoside-induced deafness,and m.1555A>G,m.827A>G and m.1005T>C are the most likely pathogenic mutations in aminoglycoside-induced deafness.