Novel duplication mutation of EYA1 causes branchio-oto-renal syndrome in a Chinese family
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摘要: 目的 为一临床诊断为鳃-耳-肾综合征的中国家系寻找致病基因及位点。 方法 回顾性分析1个鳃-耳-肾综合征核心家系的临床特征及治疗经过；应用全外显子测序技术(WES)对先证者进行全外显子水平突变分析，其中部分外显子缺失/重复利用荧光定量PCR方法(Realtime-PCR)验证。 结果 该家系中先证者，男，4岁1个月，有耳聋、内耳和中耳结构畸形、耳前瘘管、鳃裂瘘管和肾萎缩临床表型，符合鳃-耳-肾综合征的临床诊断，父、母均无类似表型。WES检测及荧光定量PCR验证发现患者EYA1基因外显子13~18存在单倍重复，其父母未见异常。外科手术切除双侧耳前及鳃裂瘘管，术后恢复较好，佩戴助听器辅助听力。 结论 本研究寻找到一种新的EYA1 基因外显子重复变异致鳃-耳-肾综合征，拓展了EYA1 基因的突变谱。Abstract: Objective To identify novel genetic causes of branchio-oto-renal (BOR) syndrome in a Chinese family. Methods Clinical characteristics and treatment of a family with a BOR syndrome were retrospectively analyzed. Genetic analysis was conducted by trio whole exome sequencing (WES) and the duplicated exons were verified by fluorescence quantitative PCR (real-time PCR). Results In this family, the affected individual had deafness, structural malformation of inner ear and middle ear, pre-auricular fistula, cervical fistula and renal atrophy consistent with the clinical diagnosis of BOR syndrome. Neither the father nor the mother had similar phenotype. WES and quantitative fluorescent PCR revealed that the patient had a de novo partial duplication involving exons 13 to 18 of EYA1 gene. This mutation has not been reported in literature or any database. Bilateral pre-auricular fistulas and cervical fistulas were surgically removed and the surgery wound healed well, while hearing AIDS had been worn to assist hearing. Conclusion This study is the first to detect a novel de novo partial duplication (exons13-18) of EYA1 gene leading to BOR syndrome, and expands the mutant spectrum of EYA1 gene in Chinese population.
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Key words:
- branchio-oto-renal syndrome /
- EYA1 gene /
- copy number variation
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