线粒体A1555G异质变异来源及其与听力损失程度的相关性  

Origin of mitochondrial A1555G heterogeneous mutation and its correlation with hearing loss severity

作　　者：陈一锦 黄莎莎[1] 董国杰 康东洋[1] 袁永一[1] Chen Yijin;Huang Shasha;Dong Guojie;Kang Dongyang;Yuan Yongyi(Senior Department of Otolaryngology Head and Neck Surgery,the Sixth Medical Center of Chinese PLA General Hospital/State Key Laboratory of Hearing and Balance Science/National Clinical Research Center for Otolaryngologic Diseases/Key Laboratory of Hearing Science,Ministry of Education/Beijing Key Laboratory of Hearing Impairment Prevention and Treatment,Beijing 100048,China)

机构地区：[1]解放军总医院第六医学中心耳鼻咽喉头颈外科医学部,听觉与平衡觉全国重点实验室,国家耳鼻咽喉疾病临床医学研究中心,聋病教育部重点实验室,聋病防治北京市重点实验室,北京100048

出　　处：《中华医学杂志》2025年第6期446-451,共6页National Medical Journal of China

基　　金：国家重点研发计划(2022YFC2703602);国家自然科学基金(82271177,82271185);北京市自然科学基金(7242137)。

摘　　要：目的探讨线粒体A1555G异质变异来源及其与听力损失程度的相关性。方法本研究为横断面研究。选取2020年1月至2023年12月于解放军总医院聋病分子诊断中心行新生儿耳聋基因筛查的携带线粒体A1555G变异的个体,分析异质和均质变异占比;选取2016年1月至2023年12月在解放军总医院耳鼻咽喉头颈外科医学部门诊数据库中应用二代测序技术明确突变负荷的线粒体A1555G异质变异个体,分析其遗传来源和表型特征;并分析明确突变负荷和听力表型的线粒体A1555G变异个体的听力损失程度与A1555G突变负荷的相关性。结果在65942例新生儿中携带A1555G变异的个体共157例(男63例,女94例),人群占比2.4‰(157/65942);其中携带异质变异48例,人群占比0.7‰(48/65942);携带A1555G变异个体中异质变异占比30.6%(48/157)。A1555G异质变异个体中有5例新生变异,14例明确了突变负荷,突变负荷范围1.0%~99.4%,2例表现为双侧极重度听力损失,1例表现为单侧极重度听力损失。分析包括本研究异质变异个体在内的118例明确了A1555G突变负荷和听力表型的病例结果显示,听力损失程度与突变负荷呈正相关(r s=0.489,95%CI:0.350~0.606,P<0.001),且中重度以上听力损失个体的突变负荷均>50%(52/52)。结论A1555G异质变异的部分遗传来源为新生变异,携带A1555G异质变异的个体突变负荷区间大,且听力损失程度(尤其中重度以上)与突变负荷呈正相关。ObjectiveTo explore the genesis of the mitochondrial A1555G mutation and its correlation with the severity of hearing impairment.MethodsA cross-sectional study was conducted.Individuals with the mitochondrial A1555G mutation who were screened for neonatal deafness genes at the Molecular Diagnostic Center for Deafness,PLA General Hospital,between January 2020 and December 2023 were selected to analyze the proportions of heterogeneous and homogeneous variants.Meanwhile,individuals with the mitochondrial A1555G heterogeneous mutation identified through next-generation sequencing in the outpatient database of the Department of Otolaryngology,Head and Neck Surgery,PLA General Hospital from January 2016 to December 2023 were selected for analysis of their genetic origins and phenotypic characteristics.The correlation between the severity of hearing loss and the A1555G mutation load was further explored by examining individuals with known mutation load and their corresponding hearing phenotypes.ResultsAmong the 65942 newborns,157 individuals(63 males and 94 females)were found to carry the A1555G mutation(2.4 per thousand individuals)(157/65942).There were 48 individuals carrying heterogeneous mutation(7 per ten thousand individuals)(48/65942),and 30.6%(48/157)of the individuals carrying A1555G mutation had heterogeneous mutation.Among the A1555G heteroplasmy individuals,there were five cases of neonatal mutation,14 cases of clear mutation load,and the mutation load ranged from 1.0%to 99.4%.Two cases showed bilateral extremely severe hearing loss,and one case exhibited unilateral extremely severe hearing loss.Analysis of 118 cases involving the A1555G mutation load and hearing phenotype,including heteroplasmy individuals,revealed a positive correlation between the degree of hearing loss and the mutation load(r s=0.489,95%CI:0.350-0.606,P<0.001).Additionally,the mutation load in individuals with moderate to severe hearing loss was greater than 50%in all cases(52/52).ConclusionsThe current study indicates that some of the

关 键 词：聋 线粒体DNA变异 突变负荷 新生变异 二代测序 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]