Iván Martín Castillo , Elvira Mora , Rafael Hernani , Jose V. Cervera , María J. Fernandez , Blanca Ferrer-Lores , Esperanza Such , Marisa Calabuig , Rosario Abellán , Marina Díaz-Beyá , Juan C. Hernández-Boluda , Carlos Solano , Eva Villamón , Mar Tormo
{"title":"VEXAS综合征中UBA1突变的快速筛选和监测。","authors":"Iván Martín Castillo , Elvira Mora , Rafael Hernani , Jose V. Cervera , María J. Fernandez , Blanca Ferrer-Lores , Esperanza Such , Marisa Calabuig , Rosario Abellán , Marina Díaz-Beyá , Juan C. Hernández-Boluda , Carlos Solano , Eva Villamón , Mar Tormo","doi":"10.1016/j.jmoldx.2025.03.004","DOIUrl":null,"url":null,"abstract":"<div><div>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a severe adult-onset autoinflammatory disease associated with hematologic conditions, such as myelodysplastic syndrome. VEXAS is mostly due to an acquired mutation affecting methionine 41 (p.M41) of the <em>UBA1</em> gene, which is present in >90% of patients and usually at a high burden. Treatment strategies are diverse, but many aim to suppress the <em>UBA1</em> mutant clone with hypomethylating agents or by allogeneic hematopoietic cell transplantation. In the present study, we have developed a high-resolution melting tool for rapid detection of <em>UBA1</em> p.M41 mutations, useful in diagnostic discrimination, and three sensitive real-time allele-specific oligonucleotide PCRs to determine the variant allele frequency of p.M41T/V/L mutations, applicable in the molecular monitoring of the disease.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 6","pages":"Pages 431-437"},"PeriodicalIF":3.4000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rapid Screening and Monitoring of UBA1 Mutations in VEXAS Syndrome\",\"authors\":\"Iván Martín Castillo , Elvira Mora , Rafael Hernani , Jose V. Cervera , María J. Fernandez , Blanca Ferrer-Lores , Esperanza Such , Marisa Calabuig , Rosario Abellán , Marina Díaz-Beyá , Juan C. Hernández-Boluda , Carlos Solano , Eva Villamón , Mar Tormo\",\"doi\":\"10.1016/j.jmoldx.2025.03.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a severe adult-onset autoinflammatory disease associated with hematologic conditions, such as myelodysplastic syndrome. VEXAS is mostly due to an acquired mutation affecting methionine 41 (p.M41) of the <em>UBA1</em> gene, which is present in >90% of patients and usually at a high burden. Treatment strategies are diverse, but many aim to suppress the <em>UBA1</em> mutant clone with hypomethylating agents or by allogeneic hematopoietic cell transplantation. In the present study, we have developed a high-resolution melting tool for rapid detection of <em>UBA1</em> p.M41 mutations, useful in diagnostic discrimination, and three sensitive real-time allele-specific oligonucleotide PCRs to determine the variant allele frequency of p.M41T/V/L mutations, applicable in the molecular monitoring of the disease.</div></div>\",\"PeriodicalId\":50128,\"journal\":{\"name\":\"Journal of Molecular Diagnostics\",\"volume\":\"27 6\",\"pages\":\"Pages 431-437\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-04-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Diagnostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1525157825000844\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Diagnostics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1525157825000844","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Rapid Screening and Monitoring of UBA1 Mutations in VEXAS Syndrome
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a severe adult-onset autoinflammatory disease associated with hematologic conditions, such as myelodysplastic syndrome. VEXAS is mostly due to an acquired mutation affecting methionine 41 (p.M41) of the UBA1 gene, which is present in >90% of patients and usually at a high burden. Treatment strategies are diverse, but many aim to suppress the UBA1 mutant clone with hypomethylating agents or by allogeneic hematopoietic cell transplantation. In the present study, we have developed a high-resolution melting tool for rapid detection of UBA1 p.M41 mutations, useful in diagnostic discrimination, and three sensitive real-time allele-specific oligonucleotide PCRs to determine the variant allele frequency of p.M41T/V/L mutations, applicable in the molecular monitoring of the disease.
期刊介绍:
The Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology (AMP), co-owned by the American Society for Investigative Pathology (ASIP), seeks to publish high quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine. The editors welcome for review articles that contain: novel discoveries or clinicopathologic correlations including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, clinical informatics, or the description of polymorphisms linked to disease states or normal variations; the application of diagnostic methodologies in clinical trials; or the development of new or improved molecular methods which may be applied to diagnosis or monitoring of disease or disease predisposition.