一个遗传性听神经病伴视神经萎缩家系研究  

A Pedigree Study of Hereditary Auditory Neuropathy with Optic Atrophy

作　　者：董佩 索利敏[1] 张磊[1] 何敏[2] 贾薇 李通 范林静 李青峰[1] 杨洁[1] 靳玲[1] 李丹[1] 薛金梅[1] 赵长青[1] 张亚茜 段建雄 Dong Pei;Suo Limin;Zhang Lei;He Min;Jia Wei;Li Tong;Fan Linjing;Li Qingfeng;Yang Jie;Jin Ling;Li Dan;Xue Jinmei;Zhao Changqing;Zhang Yaxi;Duan Jianxiong(Department of Otolaryngology-Head and Neck Surgery,Shanxi Provincial Key Cultivation Laboratory for Neuroimmunity Research of Airway Inflammatory Diseases,the Second Hospital of Shanxi Medical University,Taiyuan,030000,China;不详)

机构地区：[1]山西医科大学第二医院耳鼻咽喉头颈外科,山西省气道炎性疾病神经免疫研究省级重点培育实验室,太原030000 [2]山西医科大学第二医院眼科 [3]山西医科大学基础医学院生物化学与分子生物学教研室 [4]山西国信凯尔医学检验所

出　　处：《听力学及言语疾病杂志》2024年第2期107-111,共5页Journal of Audiology and Speech Pathology

基　　金：山西省重点研发计划项目(201803D31122);山西省留学人员科技活动择优资助项目(2019-39)。

摘　　要：目的 研究探讨一个听神经病伴视神经萎缩家系遗传性致病原因。方法 详细询问先证者病史及家族史、进行临床相关检查确诊听神经病伴视神经萎缩,绘制该家系遗传系谱。抽取先证者(Ⅲ-7)外周血行全外显子组测序,对检出的突变进行致病性判读,对先证者妻子(Ⅲ-8)、大女儿(Ⅳ-7)、二女儿(Ⅳ-9)和儿子(Ⅳ-10)进行Sanger测序验证突变位点,并结合临床表现和检查结果进行研究。结果 该家系遗传方式为常染色体显性遗传,先证者(Ⅲ-7)19岁时出现视力下降,30岁时出现双侧感音神经性聋,言语识别率下降,其所在5代20人大家系中10人(2人已故)有类似听力及视力下降症状。先证者(Ⅲ-7)、大女儿(Ⅳ-7)和儿子(Ⅳ-10)听力学检查:纯音测听示双侧感音神经性聋,ABR双耳未引出,40 Hz相关电位(AERP)双耳均未引出,OAE部分或全部频率可引出,镫骨肌声反射阈值未引出;Ⅲ-7、Ⅳ-10眼底检查有不同程度视乳头萎缩,OCT示双眼视盘神经纤维层厚度变薄、视觉诱发电位示P100波峰时延长,确诊为遗传性听神经病伴视神经萎缩。Ⅲ-7行全外显子检测发现3号染色体有一个致病位点OPA1基因c.1334G>A(p.Arg445His,NM_015560.2)突变,一代测序结果示Ⅳ-7和Ⅳ-10也有该突变,Ⅲ-8和Ⅳ-9该位点的基因型是野生纯合型,即未发生突变。结论 OPA1基因c.1334G>A(p.Arg445His,NM_015560.2)突变位点为该家系致病突变。Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examinations were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7) was collected for whole exome sequencing,and the pathogenicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9) and son(Ⅳ-10) were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deafness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased) showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7) and son(Ⅳ-10) underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasonable in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed prolonged P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G>A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G>A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 an

关 键 词：听神经病 遗传性视神经萎缩 OPA1基因 

分 类 号：R764.4[医药卫生—耳鼻咽喉科]