Van der Hoeve综合征型耳聋患者COL1A1基因变异分析及临床防治探讨  

Analysis of COL1A1 gene variation and clinical prevention and treatment in patients with Van der Hoeve syndrome

作　　者：黄爱萍 高松[3] 黄莎莎 王国建[1] 韩东一[1] 戴朴[1] 袁永一[1] Huang Aiping;Gao Song;Huang Shasha;Wang Guojian;Han Dongyi;Dai Pu;Yuan Yongyi(College of Otolaryngology Head and Neck Surgery,Chinese People′s Liberation Army General Hospital,Chinese People′s Liberation Army Medical School National Clinical Research Center for Otolaryngologic Diseases State Key Lab of Hearing Science,Ministry of Education,Beijing 100853,China;Department of Otolaryngology,Children's Hospital of Hebei Province,Shijiazhuang 050030,Hebei Province,China;Department of Otolaryngology,Joint Logistic Support Force 909th Hospital,Zhangzhou 363000,Fujian Province,China)

机构地区：[1]解放军总医院耳鼻咽喉头颈外科医学部,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,北京100853 [2]河北省儿童医院耳鼻咽喉科,石家庄050030 [3]联勤保障部队第九〇九医院耳鼻咽喉科,福建省漳州市363000

出　　处：《中华耳鼻咽喉头颈外科杂志》2021年第12期1292-1299,共8页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家重点研发计划(2016YFC1000706,2016YFC1000704);国家自然科学基金重点项目(81730029);国家自然科学基金面上项目(81873704);北京市自然科学基金重点项目(7191011);解放军总医院杰青培育专项(2017-JQPY-001)。

摘　　要：目的探讨Van der Hoeve综合征的临床表型、治疗和预防以及致病基因COL1A1的变异特点。方法回顾性分析2008年1月至2020年10月在解放军总医院进行耳聋基因检测的综合征型耳聋患者的听力及测序数据,总结COL1A1基因的变异情况,对可追踪的患者及家庭进行回访,总结分析其病情进展及临床治疗效果,对预防策略进行探讨。结果共7例携带COL1A1基因变异的耳聋患者进行了遗传学检测及临床治疗,7例患者的变异位点分别为c.1342A>T(p.Lys448*)、c.124C>T(p.Gln42*)、c.249insG(p.Ala84*)、c.668insC(p.Gly224*)、c.2829+1G>C、c.1081C>T(p.Arg361*)、c.1792C>T(p.Arg598*),其中c.1081C>T、c.1792C>T既往已有报道,余5个位点为尚未见报道的新变异。对7例先证者均行人工镫骨植入术,并进行相应的遗传咨询及预防指导。结论Van der Hoeve综合征属于成骨不全Ⅰ型,致病基因COL1A1存在几种基因变异,该病外显率高,对于逐渐加重的听力下降,可以通过外科干预改善患者的生活质量,通过精准的遗传咨询及胚胎植入前诊断进行一级预防。Objective To investigate the clinical phenotype,treatment and prevention of Van der Hoeve syndrome,and analyze the variation characteristics of its related gene COL1A1.Methods Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People′s Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed.The variation of the COL1A1 gene and return visits to traceable patients and families were summarized,the disease progress and clinical treatment effects were analyzed,and the prevention strategies were discussed.Results A total of 7 patients with COL1A1 gene mutation underwent clinical intervention.The mutation sites were c.1342A>T(p.Lys448*),c.124C>T(p.Gln42*),c.249insG(p.Ala84*),c.668insC(p.Gly224*),c.2829+1G>C,c.1081C>T(p.Arg361*),c.1792C>T(p.Arg598*),of which c.1081C>T and c.1792C>T had been previously reported,and the remaining 5 were novo mutations that have not been reported.All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance.Conclusions Van der Hoeve syndrome belongs to osteogenesis imperfecta typeⅠ.The disease has high penetrance.Timely surgical intervention for hearing loss can improve the life quality in patients.Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.

关 键 词：Van der Hoeve综合征 成骨不全 COL1A1基因 镫骨外科手术 遗传咨询 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]