变异的基因型-表型分析：62个中国家系报告及文献综述
Genotype-Phenotype Analysis of Variations: Reporting of 62 Chinese Families and a Literature Review.
作者信息
Yang Junxing, Zhou Lin, Ouyang Jiamin, Xiao Xueshan, Sun Wenmin, Li Shiqiang, Zhang Qingjiong
机构信息
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
出版信息
Front Genet. 2021 Jun 23;12:600210. doi: 10.3389/fgene.2021.600210. eCollection 2021.
PURPOSE
is the most common cause of X-linked retinitis pigmentosa (RP), of which female carriers are also frequently affected. The aim of the current study was to explore the variation spectrum and associated phenotype based on the data from our lab and previous studies.
METHODS
Variants in were selected from exome sequencing data of 7,092 probands with different eye conditions. The probands and their available family members underwent comprehensive ocular examinations. Similar data were collected from previous reports through searches in PubMed, Web of Science, and Google Scholar. Systematic analyses of genotypes, phenotypes and their correlations were performed.
RESULTS
A total of 46 likely pathogenic variants, including nine missense and one in-frame variants in RCC1-like domain and 36 truncation variants, in were detected in 62 unrelated families in our in-house cohort. In addition, a total of 585 variants, including 491 (83.9%) truncation variants, were identified from the literature. Systematic analysis of variants from our in-house dataset, literature, and gnomAD suggested that most of the pathogenic variants of were truncation variants while pathogenic missense and in-frame variants were enriched in the RCC1-like domain. Phenotypic variations were present between males and female carriers, including more severe refractive error but better best corrected visual acuity (BCVA) in female carriers than those in males. The male patients showed a significant reduction of BCVA with increase of age and males with exon1-14 variants presented a better BCVA than those with ORF15 variants. For female carriers, the BCVA also showed significant reduction with increase of age, but BCVA in females with exon1-14 variants was not significant difference compared with those with ORF15 variants.
CONCLUSION
Most pathogenic variants of are truncations. Missense and in-frame variants located outside of the RCC1-like domain might be benign and the pathogenicity criteria for these variants should be considered with greater caution. The BCVA and refractive error are different between males and female carriers. Increase of age and location of variants in ORF15 contribute to the reduction of BCVA in males. These results are valuable for understanding genotypes and phenotypes of
目的
[基因名称]是X连锁视网膜色素变性（RP）最常见的病因，女性携带者也常受影响。本研究旨在基于我们实验室的数据和以往研究，探索其变异谱及相关表型。
方法
从7092例患有不同眼部疾病的先证者的外显子组测序数据中筛选[基因名称]的变异。先证者及其可获得的家庭成员接受了全面的眼部检查。通过在PubMed、Web of Science和谷歌学术搜索，从以往报告中收集类似数据。对基因型、表型及其相关性进行系统分析。
结果
在我们的内部队列中，62个无关家庭中检测到[基因名称]共有46个可能的致病变异，包括RCC1样结构域中的9个错义变异和1个框内变异以及36个截短变异。此外，从文献中鉴定出总共585个变异，其中包括491个（83.9%）截短变异。对我们内部数据集、文献和gnomAD中的变异进行系统分析表明，[基因名称]的大多数致病变异是截短变异，而致病性错义变异和框内变异在RCC1样结构域中富集。男性和女性携带者之间存在表型差异，包括女性携带者的屈光不正比男性更严重，但最佳矫正视力（BCVA）更好。男性患者的BCVA随年龄增长显著降低，外显子1 - 14变异的男性患者的BCVA比具有ORF15变异的患者更好。对于女性携带者，BCVA也随年龄增长显著降低，但外显子1 - 14变异的女性与具有ORF15变异的女性相比，BCVA无显著差异。
结论
[基因名称]的大多数致病变异是截短变异。位于RCC1样结构域之外的错义变异和框内变异可能是良性的，这些变异的致病性标准应更谨慎地考虑。男性和女性携带者的BCVA和屈光不正不同。年龄增长和ORF15中变异的位置导致男性BCVA降低。这些结果对于理解[基因名称]的基因型和表型具有重要价值
Zotero 插件