IF 3.1 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Frontiers in Medicine Pub Date : 2025-02-24 eCollection Date: 2025-01-01 DOI:10.3389/fmed.2025.1472186
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
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摘要

背景:阵发性夜间血红蛋白尿症(PNH阵发性夜间血红蛋白尿症(PNH)是一种罕见的克隆性造血干细胞疾病,其特点是磷脂酰肌醇聚糖 A 类(PIG-A)基因获得性异常:本研究使用聚合酶链反应(PCR)分析了 31 名巴西 PNH 患者的 PIG-A 基因,然后进行了 Sanger 测序,其中包括 23 名典型 PNH 患者和 8 名亚临床 PNH 患者(再生障碍性贫血和 PNH 克隆):结果:发现了多种获得性 PIG-A 变异,包括插入、缺失和单碱基置换。发现的大多数变体(29 个中的 17 个)被认为可能是阵发性夜间血红蛋白尿症(PNH)的致病变体。六个变异体的意义未定,六个变异体可能是良性的。体细胞变异的类型和位置在患者中表现出差异性,以小缺失和简单碱基变化为主。值得注意的是,41%的变异为框架移位,35%为错义。在 23 例溶血性 PNH 患者中,19 例至少有一个可检测到的致病变异。亚临床型 PNH 病例仅以多态性为特征:总之,巴西 PNH 患者的体细胞变异在位点分布和类型上都存在差异。与以往研究中观察到的变异热点相反,本研究未发现任何变异热点。溶血性 PNH 患者的临床特征与其变异之间没有发现特定的相关性,这可能是由于变异种类繁多所致。
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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.

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来源期刊
Frontiers in Medicine
Frontiers in Medicine Medicine-General Medicine
CiteScore
5.10
自引率
5.10%
发文量
3710
审稿时长
12 weeks
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. In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate - the use of patient-reported outcomes under real world conditions - the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines - the scientific bases for guidelines and decisions from regulatory authorities - access to medicinal products and medical devices worldwide - addressing the grand health challenges around the world
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