Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing
Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing
复制标题
下一代测序揭示了一大群遗传性视网膜营养不良患者的基因型-表型相关性和突变谱
DOI：
10.1038/gim.2014.138
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发表时间：
2015-04-01
影响因子：
8.8
通讯作者：
Jin, Zi-Bing
中科院分区：
文献类型：
--
作者：
Huang, Xiu-Feng;Huang, Fang;Jin, Zi-Bing
目的：遗传性视网膜营养不良（IRD）是世界范围内致盲的主要原因。由于IRD的高度遗传异质性，其病因和基因型谱尚未明确，基因型-表型相关性的信息也有限。本研究的目的是阐明IRD.Methods的突变谱和基因型-表型相关性：我们开发了一个有针对性的面板164个已知的视网膜疾病基因，88个候选基因，和32个视网膜丰富的microRNA，用于外显子组测序。结果：在99例无关患者中，共检测到124个已知视网膜疾病基因突变，其中79个为新突变（检出率为55.3%）。此外，发现了新的基因型-表型相关性，并注意到表型趋势。三例报道，包括AHI1作为一种新的候选基因的鉴定nonsyndromic视网膜色素变性pigmentosa.Conclusion：这项研究揭示了新的基因型-表型相关性，包括一个新的候选基因，并确定了124个遗传缺陷与IRD队列内。新的基因型-表型相关性和突变谱的鉴定大大增强了目前对IRD表型和基因型异质性的认识，这将有助于IRD患者的临床诊断和个性化治疗。
Purpose: Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD.Methods: We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited.Results: In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa.Conclusion: This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD. The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.