[Analysis of clinical manifestations and genetic characteristics of a late-onset auditory neuropathy pedigree caused by a mitochondrial

Objective: The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation. Methods: A male proband who presented with bilateral sensorineural hearing loss at Henan Children's Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family. Results: In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion: The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.