Eleanor C. Broeren , Vanessa N. Gitau , Alicia B. Byrne , Pamela Ajuyah , Marie B. Balzotti , Jonathan S. Berg , Krista Bluske , B. Monica Bowen , Matthew P. Brown , Amanda Buchanan , Brendan T. Burns , Nicole J. Burns , Anjana Chandrasekhar , Aditi Chawla , Jessica X. Chong , Maya Chopra , Amanda R. Clause , Marina T. DiStefano , Stephanie DiTroia , Marwa A. Elnagheeb , Alison J. Coffey
{"title":"ClinGen综合征疾病基因管理专家小组：评估111个基因与疾病关系的临床有效性","authors":"Eleanor C. Broeren , Vanessa N. Gitau , Alicia B. Byrne , Pamela Ajuyah , Marie B. Balzotti , Jonathan S. Berg , Krista Bluske , B. Monica Bowen , Matthew P. Brown , Amanda Buchanan , Brendan T. Burns , Nicole J. Burns , Anjana Chandrasekhar , Aditi Chawla , Jessica X. Chong , Maya Chopra , Amanda R. Clause , Marina T. DiStefano , Stephanie DiTroia , Marwa A. Elnagheeb , Alison J. Coffey","doi":"10.1016/j.gimo.2025.103429","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders Gene Curation Expert Panel (SD-GCEP) was formed to address an unmet need.</div></div><div><h3>Methods</h3><div>The SD-GCEP applied ClinGen’s framework to evaluate the clinical validity of genes associated with rare syndromic disorders. A total of 111 gene-disease relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.</div></div><div><h3>Results</h3><div>From April 2020 through March 2024, 38 precurations were performed on genes with multiple disease relationships and were reviewed to determine if the disorders were part of a spectrum or distinct entities. A total of 14 genes were lumped into a single disease entity, and 24 were split into separate entities, of which 11 were curated by the SD-GCEP. A full review of 111 GDRs for 100 genes followed, with 78 classified as Definitive, 9 as Strong, 15 as Moderate, and 9 as Limited, highlighting cases in which further data are needed. All diseases involved 2 or more organ systems, whereas the majority (88/111 GDRs, 79.2%) had 5 or more organ systems affected.</div></div><div><h3>Conclusion</h3><div>The SD-GCEP addresses a critical gap in gene curation efforts, enabling inclusion of genes for syndromic disorders in clinical testing and contributing to keeping pace with the rapid discovery of new genetic syndromes.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 103429"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease relationships\",\"authors\":\"Eleanor C. Broeren , Vanessa N. Gitau , Alicia B. Byrne , Pamela Ajuyah , Marie B. Balzotti , Jonathan S. Berg , Krista Bluske , B. Monica Bowen , Matthew P. Brown , Amanda Buchanan , Brendan T. Burns , Nicole J. Burns , Anjana Chandrasekhar , Aditi Chawla , Jessica X. Chong , Maya Chopra , Amanda R. Clause , Marina T. DiStefano , Stephanie DiTroia , Marwa A. Elnagheeb , Alison J. Coffey\",\"doi\":\"10.1016/j.gimo.2025.103429\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders Gene Curation Expert Panel (SD-GCEP) was formed to address an unmet need.</div></div><div><h3>Methods</h3><div>The SD-GCEP applied ClinGen’s framework to evaluate the clinical validity of genes associated with rare syndromic disorders. A total of 111 gene-disease relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.</div></div><div><h3>Results</h3><div>From April 2020 through March 2024, 38 precurations were performed on genes with multiple disease relationships and were reviewed to determine if the disorders were part of a spectrum or distinct entities. A total of 14 genes were lumped into a single disease entity, and 24 were split into separate entities, of which 11 were curated by the SD-GCEP. A full review of 111 GDRs for 100 genes followed, with 78 classified as Definitive, 9 as Strong, 15 as Moderate, and 9 as Limited, highlighting cases in which further data are needed. All diseases involved 2 or more organ systems, whereas the majority (88/111 GDRs, 79.2%) had 5 or more organ systems affected.</div></div><div><h3>Conclusion</h3><div>The SD-GCEP addresses a critical gap in gene curation efforts, enabling inclusion of genes for syndromic disorders in clinical testing and contributing to keeping pace with the rapid discovery of new genetic syndromes.</div></div>\",\"PeriodicalId\":100576,\"journal\":{\"name\":\"Genetics in Medicine Open\",\"volume\":\"3 \",\"pages\":\"Article 103429\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetics in Medicine Open\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2949774425014682\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics in Medicine Open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949774425014682","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease relationships
Purpose
The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders Gene Curation Expert Panel (SD-GCEP) was formed to address an unmet need.
Methods
The SD-GCEP applied ClinGen’s framework to evaluate the clinical validity of genes associated with rare syndromic disorders. A total of 111 gene-disease relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.
Results
From April 2020 through March 2024, 38 precurations were performed on genes with multiple disease relationships and were reviewed to determine if the disorders were part of a spectrum or distinct entities. A total of 14 genes were lumped into a single disease entity, and 24 were split into separate entities, of which 11 were curated by the SD-GCEP. A full review of 111 GDRs for 100 genes followed, with 78 classified as Definitive, 9 as Strong, 15 as Moderate, and 9 as Limited, highlighting cases in which further data are needed. All diseases involved 2 or more organ systems, whereas the majority (88/111 GDRs, 79.2%) had 5 or more organ systems affected.
Conclusion
The SD-GCEP addresses a critical gap in gene curation efforts, enabling inclusion of genes for syndromic disorders in clinical testing and contributing to keeping pace with the rapid discovery of new genetic syndromes.
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