Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing
Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing
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发表时间：
2015-04
期刊：
影响因子：
2.2
通讯作者：
Yan Xu;L. Guan;Xueshan Xiao;Jianguo Zhang;Shi-qiang Li;Hui Jiang;Xiao-yun Jia;Jianhua Yang
中科院分区：
文献类型：
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作者：
Yan Xu;L. Guan;Xueshan Xiao;Jianguo Zhang;Shi-qiang Li;Hui Jiang;Xiao-yun Jia;Jianhua Yang
目的对157个视网膜色素变性（RP）家系中的79个家系进行外显子组测序，检测60个已知基因的突变。这项研究分析了同一队列中与其他形式的遗传性视网膜营养不良相关的129个基因的变异。方法在已分析的73个基因基础上，利用RetNet软件筛选出129个与其他遗传性视网膜营养不良相关的基因。通过全外显子组测序确定的129个基因中的变异体被选择并通过生物信息学分析筛选。通过桑格测序确认候选变体，并通过分析可用的家族成员和对照进行验证。结果在129个基因中共发现90个候选变异。桑格测序证实了90个变异体中的83个。对家族成员和对照的分析排除了这83种变异中的76种。其余7个变异体被认为是潜在的致病突变;这些是BBS 2中的c.899A>G、c.1814C>G和c.2107C>T; INPP 5E中的c.1073C>T和c.1669C>T;以及CACNA 1F中的c.3582C>G和c.5704-5C>G。这七个突变中有六个是新的。在5名无家族史的无关患者中检测到突变，包括3名BBS 2和INPP 5E纯合或复合杂合突变患者，以及2名CACNA 1F半合子突变患者。没有一个患者有常染色体显性视网膜营养不良相关的基因突变。结论在RP患者中，只有3%（5/157）的患者存在与其他遗传性视网膜营养不良相关的129个基因的突变。
Purpose Mutations in 60 known genes were previously identified by exome sequencing in 79 of 157 families with retinitis pigmentosa (RP). This study analyzed variants in 129 genes associated with other forms of hereditary retinal dystrophy in the same cohort. Methods Apart from the 73 genes previously analyzed, a further 129 genes responsible for other forms of hereditary retinal dystrophy were selected based on RetNet. Variants in the 129 genes determined by whole exome sequencing were selected and filtered by bioinformatics analysis. Candidate variants were confirmed by Sanger sequencing and validated by analysis of available family members and controls. Results A total of 90 candidate variants were present in the 129 genes. Sanger sequencing confirmed 83 of the 90 variants. Analysis of family members and controls excluded 76 of these 83 variants. The remaining seven variants were considered to be potential pathogenic mutations; these were c.899A>G, c.1814C>G, and c.2107C>T in BBS2; c.1073C>T and c.1669C>T in INPP5E; and c.3582C>G and c.5704–5C>G in CACNA1F. Six of these seven mutations were novel. The mutations were detected in five unrelated patients without a family history, including three patients with homozygous or compound heterozygous mutations in BBS2 and INPP5E, and two patients with hemizygous mutations in CACNA1F. None of the patients had mutations in the genes associated with autosome dominant retinal dystrophy. Conclusions Only a small portion of patients with RP, about 3% (5/157), had causative mutations in the 129 genes associated with other forms of hereditary retinal dystrophy.