Usher综合征一家系的致病基因分析

Genetic analysis of a family with Usher syndrome

摘要:

目的：对一Usher综合征家系的临床特征进行分析，探索该家系的致病基因。

方法：收集于我院就诊的一视网膜色素变性家系，详细询问患者病史并进行临床检查，诊断为Usher综合征，抽取家系成员静脉血4mL，提取全基因组DNA，对先证者进行靶向捕获高通量测序获得突变位点，对于筛选出的可疑突变扩展至家系全体成员进行Sanger测序验证，同时在100名正常对照者中验证。

结果：患者除视网膜色素变性表现外，还存在轻至中度感音神经性耳聋，测序结果发现家系患者USH2A基因复合杂合突变c.2310_2311insA(p.E771Rfs*8)和c.8559-2A>G(IVS42)，而在与患者有直系血缘关系的亲属中发现仅存在其中1个突变，其他家属成员和正常人中未发现该两种突变。

结论：USH2A基因为该家系的致病基因，c.8559-2A>G(IVS42)突变为已报道的热点突变，而c.2310_2311insA(p.E771Rfs*8)突变则为首次报道，本研究扩展了USH2A基因导致Usher综合征的突变谱。

Abstract:

AIM:To analyze the clinical features of a Usher syndrome family and explore the pathogenic gene of the disease.

METHODS: A Chinese family with Usher syndrome was involved in our study. After informed consent, careful clinical examinations were taken and 4mL blood were obtained. The whole genome DNA was extracted and target-captured next generation sequencing of the proband was performed to identify suspected mutations. We used Sanger sequencing to verify the detected mutations in all the members of the family, as well as in 100 normal controls.

RESULTS: In addition to typical retinitis pigmentosa, the patients suffered from mild to moderate sensorineural deafness. Sequencing results revealed compound heterozygous mutations(c.2310_2311insA and c.8559-2A>G)of USH2A gene in the patients, and either of the mutations was found in normal relatives that had consanguinity with the patients. Both of the mutations were not found in other members of the family and normal individuals.

CONCLUSION: USH2A is the pathogenic gene of the disease in this family. The mutation c.8559-2A>G(IVS42)is a previously reported mutation, while the mutation c.2310_2311 insA(p.E771Rfs*8)is a novel mutation. The study has expanded the mutation spectrum of USH2A gene resulting in Usher syndrome.