Patricia Eiko Yamakawa, Caio Perez Gomes, Agatha Ribeiro Mendes, Caio Cesar Justino de Oliveira, Florencio Porto Freitas, Fabiana Bettoni, Ernande Xavier Dos Santos, Vinicius Campos de Molla, Matheus Vescovi Gonçalves, Jessica Branquinho, Beatriz Ribeiro Nogueira, Joao Bosco Pesquero, Celso Arrais-Rodrigues
{"title":"Somatic mutations in Brazilian patients with paroxysmal nocturnal hemoglobinuria: a comprehensive analysis.","authors":"Patricia Eiko Yamakawa, Caio Perez Gomes, Agatha Ribeiro Mendes, Caio Cesar Justino de Oliveira, Florencio Porto Freitas, Fabiana Bettoni, Ernande Xavier Dos Santos, Vinicius Campos de Molla, Matheus Vescovi Gonçalves, Jessica Branquinho, Beatriz Ribeiro Nogueira, Joao Bosco Pesquero, Celso Arrais-Rodrigues","doi":"10.3389/fmed.2025.1472186","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by acquired abnormalities in the phosphatidylinositol glycan class A (<i>PIG-A</i>) gene.</p><p><strong>Methods: </strong>This study analyzed <i>PIG-A</i> gene using polymerase chain reaction (PCR) followed by Sanger sequencing of 31 Brazilian patients with PNH, including 23 with classical PNH and 8 with subclinical PNH (aplastic anemia and a PNH clone).</p><p><strong>Results: </strong>A diverse spectrum of acquired <i>PIG-A</i> variants was identified, encompassing insertions, deletions, and single-base substitutions. The majority of variants identified (17 out of 29) were deemed likely pathogenic for paroxysmal nocturnal hemoglobinuria (PNH). Six variants have undetermined significance (VUS) and six variants are probably benign. Somatic variants exhibited variability in type and location among the patients, with a predominance of small deletions and simple base changes. Notably, 41% of the variants were frameshift and 35% were missense. Among the 23 patients with hemolytic PNH, 19 had at least one detectable pathogenic variant. Subclinical PNH cases were characterized solely by polymorphisms.</p><p><strong>Conclusion: </strong>In conclusion, the somatic variants in Brazilian PNH patients displayed variability in both site distribution and type. Contrary to mutational hotspots observed in previous studies, none were identified in this cohort. No specific correlation between the clinical characteristics of hemolytic PNH patients and their variants was found, likely due to the extensive variety of mutations.</p>","PeriodicalId":12488,"journal":{"name":"Frontiers in Medicine","volume":"12 ","pages":"1472186"},"PeriodicalIF":3.1000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891177/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fmed.2025.1472186","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Somatic mutations in Brazilian patients with paroxysmal nocturnal hemoglobinuria: a comprehensive analysis.
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by acquired abnormalities in the phosphatidylinositol glycan class A (PIG-A) gene.
Methods: This study analyzed PIG-A gene using polymerase chain reaction (PCR) followed by Sanger sequencing of 31 Brazilian patients with PNH, including 23 with classical PNH and 8 with subclinical PNH (aplastic anemia and a PNH clone).
Results: A diverse spectrum of acquired PIG-A variants was identified, encompassing insertions, deletions, and single-base substitutions. The majority of variants identified (17 out of 29) were deemed likely pathogenic for paroxysmal nocturnal hemoglobinuria (PNH). Six variants have undetermined significance (VUS) and six variants are probably benign. Somatic variants exhibited variability in type and location among the patients, with a predominance of small deletions and simple base changes. Notably, 41% of the variants were frameshift and 35% were missense. Among the 23 patients with hemolytic PNH, 19 had at least one detectable pathogenic variant. Subclinical PNH cases were characterized solely by polymorphisms.
Conclusion: In conclusion, the somatic variants in Brazilian PNH patients displayed variability in both site distribution and type. Contrary to mutational hotspots observed in previous studies, none were identified in this cohort. No specific correlation between the clinical characteristics of hemolytic PNH patients and their variants was found, likely due to the extensive variety of mutations.
期刊介绍:
Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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