Targeted next-generation sequencing reveals that a compound heterozygous mutation in phosphodiesterase 6a gene leads to retinitis pigmentosa in a Chinese family
Targeted next-generation sequencing reveals that a compound heterozygous mutation in phosphodiesterase 6a gene leads to retinitis pigmentosa in a Chinese family
复制标题
靶向二代测序揭示磷酸二酯酶6a基因复合杂合突变导致中国家族色素性视网膜炎
DOI：
10.1080/13816810.2018.1461912
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发表时间：
2018-04
影响因子：
1.2
通讯作者：
Zhang Lin
中科院分区：
文献类型：
--
作者：
Zhang Shanshan;Li Jie;Li Shujin;Yang Yeming;Yang Mu;Yang Zhenglin;Zhu Xianjun;Zhang Lin
摘要目的：视网膜色素变性（RP）是一种遗传异质性疾病，迄今已鉴定出70多个致病基因。然而，大约40%的RP病例在遗传学上仍未解决，这表明许多新的致病突变尚未被确定。本研究的目的是鉴定一个中国RP家系的致病突变。研究方法：对涉及遗传性视网膜疾病的总共163个基因进行了靶向下一代测序（NGS），以筛选可能的致病突变。桑格测序用于验证突变。结果：我们鉴定了两个杂合突变：剪接位点突变c.1407 + 1G>C和无义突变c。RP患者磷酸二酯酶6A（PDE6A）基因中的1957C>T（p.R653X）。这两个突变分别遗传自他的父亲和母亲。此外，这些突变在我们的内部数据库中是独特的，在人类基因组数据库中是罕见的，这意味着这两个突变是病理性的。结论：应用靶向NGS方法，我们在一个中国人RP家系中发现了PDE6A基因的复合杂合突变。
ABSTRACT Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous disease with over 70 causative genes identified to date. However, approximately 40% of RP cases remain genetically unsolved, suggesting that many novel disease-causing mutations are yet to be identified. The purpose of this study is to identify the causative mutations of a Chinese RP family. Methods: Targeted next-generation sequencing (NGS) for a total of 163 genes which involved in inherited retinal disorders were used to screen the possible causative mutations. Sanger sequencing was used to verify the mutations. Results: As results, we identified two heterozygous mutations: a splicing site mutation c.1407 + 1G>C and a nonsense mutation c. 1957C>T (p.R653X) in phosphodiesterase 6A (PDE6A) gene in the RP patient. These two mutations are inherited from his father and mother, respectively. Furthermore, these mutations are unique in our in-house database and are rare in human genome databases, implicating that these two mutations are pathological. Conclusion: By using targeted NGS method, we identified a compound heterozygous mutation in PDE6A gene that is associated with RP in a Chinese family.
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DOI：
--
发表时间：
2017-01
期刊：
--
影响因子：
--
作者：
Abigail T. Fahim;S. Daiger;R. Weleber
通讯作者：
Abigail T. Fahim;S. Daiger;R. Weleber
影响因子：
5.6
作者：
He Y;Zhang Y;Liu X;Ghazaryan E;Li Y;Xie J;Su G
通讯作者：
Su G
影响因子：
4.2
作者：
Tsang, Stephen H.;Tsui, Irena;Chou, Chai Lin;Zernant, Jana;Haamer, Eneli;Iranmanesh, Reza;Tosi, Joaquin;Allikmets, Rando
通讯作者：
Allikmets, Rando
影响因子：
56.9
作者：
KAJIWARA, K;BERSON, EL;DRYJA, TP
通讯作者：
DRYJA, TP
影响因子：
3.5
作者：
J. Reiners;E. van Wijk;Tina Märker;U. Zimmermann;Karin Jürgens;H. te Brinke;N. Overlack;R. Roepman;M. Knipper;H. Kremer;U. Wolfrum
通讯作者：
J. Reiners;E. van Wijk;Tina Märker;U. Zimmermann;Karin Jürgens;H. te Brinke;N. Overlack;R. Roepman;M. Knipper;H. Kremer;U. Wolfrum