Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing.
Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing.
复制标题
通过靶向捕获和二代测序在中国色素性视网膜炎家系中发现 CRB1 基因的新突变
DOI：
10.18632/oncotarget.12971
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发表时间：
2016-11-29
期刊：
影响因子：
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通讯作者：
Liu X
中科院分区：
文献类型：
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作者：
Lu L;Wang X;Lo D;Weng J;Liu X;Yang J;He F;Wang Y;Liu X
目的检测一个常染色体隐性遗传视网膜色素变性（ARRP）家系的致病基因。方法对该家系的所有受试者进行全面的眼科检查。对先证者进行靶向捕获下一代测序（NGS）以检测变异。通过PCR扩增和桑格测序，在其余家族成员中验证所有变体。结果该家系所有患者均诊断为视网膜色素变性（RP）。CRB1基因的c.138delA（p.Asp47IlefsX24）和c.1841G>T（p.Gly614Val）复合杂合突变在所有受影响的患者中被鉴定，但在该家族中未受影响的个体中未被鉴定。这些突变分别遗传自其父母。结论采用靶向捕获下一代测序技术，在一个中国人ARRP家系中发现了CRB1新的复合杂合突变。在评估了显著的遗传和受损的蛋白质功能后，复合杂合c.138delA（p.Asp47IlefsX24）和c.1841G>T（p.Gly614Val）突变是该家系早发性ARRP的致病基因。据我们所知，以前没有关于复合突变的报道。
PURPOSE To detect the disease-causing gene in a Chinese pedigree with autosomal-recessive retinitis pigmentosa (ARRP). METHODS All subjects in this family underwent a complete ophthalmic examination. Targeted-capture next generation sequencing (NGS) was performed on the proband to detect variants. All variants were verified in the remaining family members by PCR amplification and Sanger sequencing. RESULTS All the affected subjects in this pedigree were diagnosed with retinitis pigmentosa (RP). The compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations in the Crumbs homolog 1 (CRB1) gene were identified in all the affected patients but not in the unaffected individuals in this family. These mutations were inherited from their parents, respectively. CONCLUSION The novel compound heterozygous mutations in CRB1 were identified in a Chinese pedigree with ARRP using targeted-capture next generation sequencing. After evaluating the significant heredity and impaired protein function, the compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations are the causal genes of early onset ARRP in this pedigree. To the best of our knowledge, there is no previous report regarding the compound mutations.