Identification of four novel mutations in MYO7A gene and their association with nonsyndromic deafness and Usher Syndrome 1B
Identification of four novel mutations in MYO7A gene and their association with nonsyndromic deafness and Usher Syndrome 1B
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MYO7A 基因的四种新突变的鉴定及其与非综合征性耳聋和亚瑟综合征 1B 的关联
DOI：
10.1016/j.ijporl.2019.02.021
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发表时间：
2019-05-01
影响因子：
1.5
通讯作者：
Zhu, Baosheng
中科院分区：
文献类型：
--
作者：
Li, Yunlong;Su, Jie;Zhu, Baosheng
引言：MYO7A基因已被证明与1B型乌谢尔综合征和非综合征性耳聋有关。尽管在MYO7A基因中已经报道了许多突变，但新的MYO7A突变仍在不断被发现。
方法：分别对两名患有1B型乌谢尔综合征和非综合征性耳聋且无亲缘关系的患者进行靶向新一代测序。通过桑格测序进一步验证靶向新一代测序所确定的突变，并使用SIFT、Polyphen - 2、PyMOL、I - Mutant 2.0等生物信息学工具进行分析。
结果：通过分析这两名患者的测序数据，发现了四个新的MYO7A突变：（i）MYO7A p.Tyr560Ser和p.Ala2039Pro与1B型乌谢尔综合征有关。（ii）MYO7A c.2187 + 2(-)+ 8 delTGAGCAC和p.Leu728Pro与非综合征性听力损失有关。通过分离分析、保守性分析和生物信息学工具进一步证明这些突变可能是致病的。
结论：本研究中确定了四个新的MYO7A突变。这些发现为1B型乌谢尔综合征和非综合征性耳聋的遗传咨询提供了新的依据。
Introduction: MYO7A gene has been shown to be associated with Usher syndrome 1B and nonsyndromic deafness. Although a lot of mutations have been reported in MYO7A gene, novel MYO7A mutations are continuously to be identified.Methods: Targeted next generation sequencing was performed on the two unrelated patients with Usher syndrome 1B and nonsyndromic deafness respectively. The identified mutations from targeted next generation sequencing were further validated by Sanger sequencing, and analyzed by bioinformatics tools, like SIFT, Polyphen-2, PyMOL, I-Mutant 2.0 and so on.Results: By analyzing the sequencing data of these two patients, four novel MYO7A mutations were revealed: (i) MYO7A p.Tyr560Ser and p.Ala2039Pro were associated with Usher syndrome 1B. (ii) MYO7A c.2187 + 2(-)+ 8 delTGAGCAC and p.Leu728Pro were related to nonsyndromic hearing loss. These mutations were further proved to be possibly disease-causing by segregation analysis, conservation analysis and bioinformatics tools.Conclusions: Four novel MYO7A mutations were identified in the present study. These findings provided new evidence for the genetic counseling of Usher syndrome 1B and nonsyndromic deafness.