On August 17th, the reporter learned from Fudan University Affiliated Eye, Ear, Nose and Throat Hospital that the research results led by Professor Shu Yilai's team and jointly completed by the team of Seoul National University Hospital in South Korea provide a potential precise treatment strategy for genetic hearing loss. Deafness is one of the most common sensory disorders. According to the World Health Organization, there are approximately 430 million people worldwide suffering from disabling hearing impairment, accounting for 5% of the world's total population. Currently, there are over 200 known deafness genes, but there are currently no clinical treatment drugs available. In recent years, a study based on a large cohort of children with mild to moderate sensorineural hearing loss (SNHL) has shown that mutations in the MPZL2 gene are a common gene leading to hereditary mild to moderate SNHL. Mutations at certain specific loci in the MPZL2 gene have ancestral effects in East Asian populations, suggesting that they may be unique genetic risk factors in the region. The joint team conducted a systematic etiological analysis of 1437 unrelated families with hereditary hearing loss based on clinical cohort studies. The team screened 234 underage patients with symmetric, mild to moderate non syndromic SNHL and identified the pathogenic genes of 155 patients. Among them, 24 cases were related to MPZL2 gene mutations, accounting for 15.5%, and 23 patients carried at least one c.220Cgt; The proportion of T allele mutations is as high as 95.8%. This suggests that the mutation may be the ancestral mutation in East Asia. The team constructed a humanized mouse model targeting the mutation site, which reproduced the auditory phenotype of deaf patients caused by the MPZL2 gene mutation in humans. The joint team also developed an adenine base editor therapy system with higher flexibility of the original interval sequence adjacent motif (PAM), which successfully corrected the abnormal expression of the MPZL2 gene, significantly restored and maintained hearing in the mouse model for at least 20 weeks, and no significant off target effects were observed. This study not only provides potential treatment strategies for genetic hearing loss, but also further expands the application scope of single base editing technology in genetic diseases. (New Society)