引起原发性肥大性骨关节病的HPGD p.Ala13Glu变体的重新分类。

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI:10.1101/mcs.a006291
Juan J Alban, Alejandra Arango-Ramirez, Jorge A Olave-Rodriguez, Jose A Nastasi-Catanese, Lisa X Rodriguez
{"title":"引起原发性肥大性骨关节病的HPGD p.Ala13Glu变体的重新分类。","authors":"Juan J Alban, Alejandra Arango-Ramirez, Jorge A Olave-Rodriguez, Jose A Nastasi-Catanese, Lisa X Rodriguez","doi":"10.1101/mcs.a006291","DOIUrl":null,"url":null,"abstract":"<p><p>Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the <i>HPGD</i> gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in <i>HPGD</i> was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for <i>HPGD</i>, all provide sufficient evidence to reclassify the <i>HPGD</i> c.38C > A, p.Ala13Glu variant as likely pathogenic.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815292/pdf/","citationCount":"0","resultStr":"{\"title\":\"Reclassification of the <i>HPGD</i> p.Ala13Glu variant causing primary hypertrophic osteoarthropathy.\",\"authors\":\"Juan J Alban, Alejandra Arango-Ramirez, Jorge A Olave-Rodriguez, Jose A Nastasi-Catanese, Lisa X Rodriguez\",\"doi\":\"10.1101/mcs.a006291\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the <i>HPGD</i> gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in <i>HPGD</i> was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for <i>HPGD</i>, all provide sufficient evidence to reclassify the <i>HPGD</i> c.38C > A, p.Ala13Glu variant as likely pathogenic.</p>\",\"PeriodicalId\":10360,\"journal\":{\"name\":\"Cold Spring Harbor Molecular Case Studies\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-01-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815292/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cold Spring Harbor Molecular Case Studies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/mcs.a006291\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor Molecular Case Studies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/mcs.a006291","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/1 0:00:00","PubModel":"Print","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

在这里,我们强调了一名31岁的男性的病例,他具有PHOA的临床特征,并在HPGD基因中携带纯合变体(c.38C>a,p.Ala13Glu),如全外显子组测序(WES)所示。这种变体以前被我们的实验室归类为VUS。然而,随后报道了另一名具有相同表型和相同纯合子变体的HPGD患者。在重新评估该变体时,gnomAD人群数据库中没有该变体,支持计算预测,观察到两名先证者的纯合性和HPGD表型的特异性,所有这些都为将HPGD c.38C>A,p.Ala13Glu变体重新归类为可能的致病性提供了充分的证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy.

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信