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

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 type Ⅰ. 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.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。.