{"title":"全外显子组测序在28个中国家族中鉴定出与视网膜色素变性有关的基因。","authors":"Chang Shen, Bing You, Yu-Ning Chen, Yang Li, Wei Li, Wen-Bin Wei","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship.</p><p><strong>Method: </strong>In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations.</p><p><strong>Result: </strong>Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: <i>USH2A</i>, <i>CYP4V2</i>, <i>PRPF31</i>, <i>RHO</i>, <i>RP1</i>, <i>CNGA1</i>, <i>CNGB1</i>, <i>EYS</i>, <i>PRPF3</i>, <i>RP2</i>, <i>RPGR</i>, and <i>TOPORS</i>. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). <i>USH2A</i> (4/20, 20%) and <i>CYP4V2</i> (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in <i>USH2A1, USH2A2</i>, <i>PRPF31</i>, <i>RP2</i>, <i>TOPORS</i>, <i>CNGB1</i>, and <i>RPGR.</i> Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in <i>CYP4V2</i>.</p><p><strong>Conclusion: </strong>Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. <i>USH2A</i> and <i>CYP4V2</i> were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/da/mv-v28-96.PMC9239900.pdf","citationCount":"0","resultStr":"{\"title\":\"Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.\",\"authors\":\"Chang Shen, Bing You, Yu-Ning Chen, Yang Li, Wei Li, Wen-Bin Wei\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship.</p><p><strong>Method: </strong>In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations.</p><p><strong>Result: </strong>Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: <i>USH2A</i>, <i>CYP4V2</i>, <i>PRPF31</i>, <i>RHO</i>, <i>RP1</i>, <i>CNGA1</i>, <i>CNGB1</i>, <i>EYS</i>, <i>PRPF3</i>, <i>RP2</i>, <i>RPGR</i>, and <i>TOPORS</i>. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). <i>USH2A</i> (4/20, 20%) and <i>CYP4V2</i> (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in <i>USH2A1, USH2A2</i>, <i>PRPF31</i>, <i>RP2</i>, <i>TOPORS</i>, <i>CNGB1</i>, and <i>RPGR.</i> Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in <i>CYP4V2</i>.</p><p><strong>Conclusion: </strong>Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. <i>USH2A</i> and <i>CYP4V2</i> were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.</p>\",\"PeriodicalId\":18866,\"journal\":{\"name\":\"Molecular Vision\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2022-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/da/mv-v28-96.PMC9239900.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Vision\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Vision","FirstCategoryId":"3","ListUrlMain":"","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.
Purpose: Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship.
Method: In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations.
Result: Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: USH2A, CYP4V2, PRPF31, RHO, RP1, CNGA1, CNGB1, EYS, PRPF3, RP2, RPGR, and TOPORS. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). USH2A (4/20, 20%) and CYP4V2 (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in USH2A1, USH2A2, PRPF31, RP2, TOPORS, CNGB1, and RPGR. Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in CYP4V2.
Conclusion: Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. USH2A and CYP4V2 were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.
期刊介绍:
Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical).
Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints.
For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.