Vianey Ordoñez-Labastida, Luis Montes-Almanza, Froylan García-Martínez, Juan C Zenteno
{"title":"全外显子组测序在疑似遗传性眼病患者中鉴定因果突变的有效性","authors":"Vianey Ordoñez-Labastida, Luis Montes-Almanza, Froylan García-Martínez, Juan C Zenteno","doi":"10.24875/RIC.22000107","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Genetic eye disorders, affecting around one in 1000 people, encompass a diverse group of diseases causing severe visual deficiency. The recent adoption of next-generation sequencing techniques, including whole-exome sequencing (WES), in medicine has greatly enhanced diagnostic rates of genetically heterogeneous diseases.</p><p><strong>Objectives: </strong>The objectives of the study were to assess the diagnostic yield of WES in a cohort of Mexican individuals with suspected genetic eye disorders and to evaluate the improvement of diagnostic rates by reanalysis of WES data in patients without an initial molecular diagnosis.</p><p><strong>Methods: </strong>A total of 90 probands with ocular anomalies of suspected genetic origin were ascertained. Patients underwent WES in leukocytic DNA. Bioinformatics analysis and Sanger sequencing were used to confirm the disease-causing variants. Only variants identified as pathogenic or likely pathogenic were considered as causal.</p><p><strong>Results: </strong>Initial analysis revealed causal mutations in 46 cases (51%). Reanalysis of WES data 12 months after first analysis resulted in the identification of additional causal variants in 6 patients (7%), increasing the molecular diagnostic yield to 58%. The highest diagnostic rates by disease categories corresponded to hereditary retinal dystrophies (77%) and to anomalies of the anterior segment of the eye (47%).</p><p><strong>Conclusions: </strong>Our study demonstrates that WES is an effective approach for genetic diagnosis of genetic ocular diseases and that reanalysis of WES data can improve the diagnostic yield.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":" ","pages":"219-226"},"PeriodicalIF":1.4000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effectiveness of Whole-Exome Sequencing for the Identification of Causal Mutations in Patients with Suspected Inherited Ocular Diseases.\",\"authors\":\"Vianey Ordoñez-Labastida, Luis Montes-Almanza, Froylan García-Martínez, Juan C Zenteno\",\"doi\":\"10.24875/RIC.22000107\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Genetic eye disorders, affecting around one in 1000 people, encompass a diverse group of diseases causing severe visual deficiency. The recent adoption of next-generation sequencing techniques, including whole-exome sequencing (WES), in medicine has greatly enhanced diagnostic rates of genetically heterogeneous diseases.</p><p><strong>Objectives: </strong>The objectives of the study were to assess the diagnostic yield of WES in a cohort of Mexican individuals with suspected genetic eye disorders and to evaluate the improvement of diagnostic rates by reanalysis of WES data in patients without an initial molecular diagnosis.</p><p><strong>Methods: </strong>A total of 90 probands with ocular anomalies of suspected genetic origin were ascertained. Patients underwent WES in leukocytic DNA. Bioinformatics analysis and Sanger sequencing were used to confirm the disease-causing variants. Only variants identified as pathogenic or likely pathogenic were considered as causal.</p><p><strong>Results: </strong>Initial analysis revealed causal mutations in 46 cases (51%). Reanalysis of WES data 12 months after first analysis resulted in the identification of additional causal variants in 6 patients (7%), increasing the molecular diagnostic yield to 58%. The highest diagnostic rates by disease categories corresponded to hereditary retinal dystrophies (77%) and to anomalies of the anterior segment of the eye (47%).</p><p><strong>Conclusions: </strong>Our study demonstrates that WES is an effective approach for genetic diagnosis of genetic ocular diseases and that reanalysis of WES data can improve the diagnostic yield.</p>\",\"PeriodicalId\":49612,\"journal\":{\"name\":\"Revista De Investigacion Clinica-Clinical and Translational Investigation\",\"volume\":\" \",\"pages\":\"219-226\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Revista De Investigacion Clinica-Clinical and Translational Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.24875/RIC.22000107\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista De Investigacion Clinica-Clinical and Translational Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.24875/RIC.22000107","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Effectiveness of Whole-Exome Sequencing for the Identification of Causal Mutations in Patients with Suspected Inherited Ocular Diseases.
Background: Genetic eye disorders, affecting around one in 1000 people, encompass a diverse group of diseases causing severe visual deficiency. The recent adoption of next-generation sequencing techniques, including whole-exome sequencing (WES), in medicine has greatly enhanced diagnostic rates of genetically heterogeneous diseases.
Objectives: The objectives of the study were to assess the diagnostic yield of WES in a cohort of Mexican individuals with suspected genetic eye disorders and to evaluate the improvement of diagnostic rates by reanalysis of WES data in patients without an initial molecular diagnosis.
Methods: A total of 90 probands with ocular anomalies of suspected genetic origin were ascertained. Patients underwent WES in leukocytic DNA. Bioinformatics analysis and Sanger sequencing were used to confirm the disease-causing variants. Only variants identified as pathogenic or likely pathogenic were considered as causal.
Results: Initial analysis revealed causal mutations in 46 cases (51%). Reanalysis of WES data 12 months after first analysis resulted in the identification of additional causal variants in 6 patients (7%), increasing the molecular diagnostic yield to 58%. The highest diagnostic rates by disease categories corresponded to hereditary retinal dystrophies (77%) and to anomalies of the anterior segment of the eye (47%).
Conclusions: Our study demonstrates that WES is an effective approach for genetic diagnosis of genetic ocular diseases and that reanalysis of WES data can improve the diagnostic yield.
期刊介绍:
The Revista de Investigación Clínica – Clinical and Translational Investigation (RIC-C&TI), publishes original clinical and biomedical research of interest to physicians in internal medicine, surgery, and any of their specialties. The Revista de Investigación Clínica – Clinical and Translational Investigation is the official journal of the National Institutes of Health of Mexico, which comprises a group of Institutes and High Specialty Hospitals belonging to the Ministery of Health. The journal is published both on-line and in printed version, appears bimonthly and publishes peer-reviewed original research articles as well as brief and in-depth reviews. All articles published are open access and can be immediately and permanently free for everyone to read and download. The journal accepts clinical and molecular research articles, short reports and reviews.
Types of manuscripts:
– Brief Communications
– Research Letters
– Original Articles
– Brief Reviews
– In-depth Reviews
– Perspectives
– Letters to the Editor