临床基因组资源（ClinGen）对听力损失相关基因的整理显示，基因与疾病的有效性随时间发生了显著变化。
ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time.
作者信息
Tshering Kezang C, DiStefano Marina T, Oza Andrea M, Ajuyah Pamela, Webb Ryan, Edoh Enyonam, Broeren Ellie, Ratliff Julie, Gitau Vanessa, Paris Kelley, Aburyyan Amal, Alexander John, Albano Victoria, Bai Donglin, Booth Kevin T A, Buonfiglio Paula I, Charfeddine Cherine, Dalamón Viviana, Castillo Ignacio Del, Moreno-Pelayo Miguel Angel, Duzkale Hatice, Dorshorst Ben, Faridi Rabia, Kenna Margaret, Lewis Morag A, Luo Minjie, Lu Yu, Mkaouar Rahma, Matsunaga Tatsuo, Nara Kiyomitsu, Pandya Arti, Redfield Shelby, Roux Isabelle, Schimmenti Lisa A, Schrauwen Isabelle, Shaaban Sherin, Shen Jun, Vona Barbara, Smith Richard J, Rehm Heidi L, Azaiez Hela, Abou Tayoun Ahmad N, Amr Sami S
机构信息
The Broad Institute of MIT and Harvard, Cambridge, MA.
The Broad Institute of MIT and Harvard, Cambridge, MA; Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge, MA.
出版信息
Genet Med. 2025 May;27(5):101392. doi: 10.1016/j.gim.2025.101392. Epub 2025 Feb 19.
PURPOSE
The Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen's semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years.
METHODS
Thirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (www.clinicalgenome.org).
RESULTS
Eight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported.
CONCLUSION
Genes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.
目的
临床基因组资源（ClinGen）听力损失基因评估专家小组于2016年成立，自那时起已使用ClinGen的半定量框架评估了174种基因-疾病关系（GDR）。ClinGen要求每2至3年对所有分类为有争议、有限、中等和强相关的GDR进行及时重新评估。
方法
35种GDR在首次评估后的2年内符合重新评估标准。使用最新的评估指南重新评估先前的证据，并进行全面的文献综述以获取新证据。重新评估结果经基因评估专家小组批准后在ClinGen网站（www.clinicalgenome.org）上发布。
结果
35种GDR中有8种（22%）改变了分类。由于新的病例证据，2种中等相关和5种强相关的GDR被升级为明确相关。在对疾病实体进行合并/拆分评估后，1种强相关被归入另一种明确相关的GDR之下。35种GDR中有27种保持不变，几乎没有新证据报告。
结论
分类为中等和强相关的基因可能会随着时间积累证据并改变其分类，而有限相关的基因则不太可能获得更多证据。这些发现凸显了重新评估在确保基因检测和研究工作纳入最新证据方面的关键作用。
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