The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease relationships

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 framew...

Full description

Saved in:
Bibliographic Details
Main 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, Amanda N. Girod, Himanshu Goel, Katie L. Golden-Grant, Thuong Ha, Ada Hamosh, Jennifer M. Huang, Madeline Y. Hughes, Saumya S. Jamuar, Sylvia Kam, Akanchha Kesari, Ai Ling Koh, Rhonda N.T. Lassiter, Sarah E. Leigh, Gabrielle Lemire, Jiin Ying Lim, Alka Malhotra, Hannah R. McCurry, Becky Milewski, Shahida Moosa, Stephen A. Murray, Emma H. Owens, Elizabeth E. Palmer, Brooke C. Palus, Mayher J. Patel, Revathi Rajkumar, Julie C. Ratliff, F. Lucy Raymond, Bruno Della Ripa Rodrigues Assis, Samin A. Sajan, Zinayida Schlachetzki, Sarah A. Schmidt, Zornitza Stark, Samuel P. Strom, Julie P. Taylor, Courtney Thaxton, Devon L. Thrush, Sabrina Toro, Kezang C. Tshering, Nicole A. Vasilevsky, Bess Wayburn, Ryan F. Webb, Anne O’Donnell-Luria, Alison J. Coffey
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Genetics in Medicine Open
Subjects:
ClinGen
Gene curation
Gene-disease relationship
Rare disease
Syndromic disorders
Online Access:http://www.sciencedirect.com/science/article/pii/S2949774425014682
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2949-7744

Similar Items