Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy.

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

引用次数: 0

Abstract

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.

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引起原发性肥大性骨关节病的HPGD p.Ala13Glu变体的重新分类。

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。

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来源期刊

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

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.