Ömer Doğru, Ceren Alavanda, Şenol Demir, Ahmet Koç, Pınar Ata
{"title":"Multigene Panel Testing Reveals Novel Variants in Hereditary Spherocytosis Patients in Türkiye","authors":"Ömer Doğru, Ceren Alavanda, Şenol Demir, Ahmet Koç, Pınar Ata","doi":"10.4274/tjh.galenos.2025.2024.0270","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the genotypic characteristics of patients with hereditary spherocytosis (HS) in Türkiye and to examine the correlation between genotype and phenotype.</p><p><strong>Materials and methods: </strong>We analyzed the cases of 18 patients admitted to the pediatric hematology outpatient clinic with hemolytic anemia, jaundice, cholelithiasis, and splenomegaly. According to the Eber classification, the patients’ clinical presentations were categorized as mild, moderate, or severe. Next-generation sequencing was used to analyze single-nucleotide and copy-number variations in all genes associated with HS via clinical exome sequencing. Relationships between the genes with detected variants and the clinical presentations of the patients were investigated.</p><p><strong>Results: </strong>In total, 21 variants were detected in 5 HS-related genes. Twelve of them were previously reported variants and 9 were novel variants. Seven of them were pathogenic and two were classified as variants of uncertain significance according to the American College of Medical Genetics and Genomics. We discuss the phenotypic effects of novel pathogenic variants in the <i>SPTA1, SPTB, ANK1, SLC4A1</i>, and <i>EPB42</i> genes. Patients with pathogenic <i>EPB42</i> and <i>SLC4A1</i> variants had less severe clinical findings compared to other gene variants according to the Eber classification. On the other hand, patients with pathogenic variants of <i>SPTA1</i> and <i>SPTB</i> had more severe clinical presentation.</p><p><strong>Conclusion: </strong>Molecular diagnosis of HS is important for treatment, prediction of the clinical outcome, and appropriate genetic counseling. Our study contributes to knowledge of the genotype-phenotype distribution of HS by introducing novel variants to the literature.</p>","PeriodicalId":23362,"journal":{"name":"Turkish Journal of Hematology","volume":" ","pages":"25-32"},"PeriodicalIF":1.5000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869149/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Turkish Journal of Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4274/tjh.galenos.2025.2024.0270","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study aimed to determine the genotypic characteristics of patients with hereditary spherocytosis (HS) in Türkiye and to examine the correlation between genotype and phenotype.
Materials and methods: We analyzed the cases of 18 patients admitted to the pediatric hematology outpatient clinic with hemolytic anemia, jaundice, cholelithiasis, and splenomegaly. According to the Eber classification, the patients’ clinical presentations were categorized as mild, moderate, or severe. Next-generation sequencing was used to analyze single-nucleotide and copy-number variations in all genes associated with HS via clinical exome sequencing. Relationships between the genes with detected variants and the clinical presentations of the patients were investigated.
Results: In total, 21 variants were detected in 5 HS-related genes. Twelve of them were previously reported variants and 9 were novel variants. Seven of them were pathogenic and two were classified as variants of uncertain significance according to the American College of Medical Genetics and Genomics. We discuss the phenotypic effects of novel pathogenic variants in the SPTA1, SPTB, ANK1, SLC4A1, and EPB42 genes. Patients with pathogenic EPB42 and SLC4A1 variants had less severe clinical findings compared to other gene variants according to the Eber classification. On the other hand, patients with pathogenic variants of SPTA1 and SPTB had more severe clinical presentation.
Conclusion: Molecular diagnosis of HS is important for treatment, prediction of the clinical outcome, and appropriate genetic counseling. Our study contributes to knowledge of the genotype-phenotype distribution of HS by introducing novel variants to the literature.
期刊介绍:
The Turkish Journal of Hematology is published quarterly (March, June, September, and December) by the Turkish Society of Hematology. It is an independent, non-profit peer-reviewed international English-language periodical encompassing subjects relevant to hematology.
The Editorial Board of The Turkish Journal of Hematology adheres to the principles of the World Association of Medical Editors (WAME), International Council of Medical Journal Editors (ICMJE), Committee on Publication Ethics (COPE), Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).
The aim of The Turkish Journal of Hematology is to publish original hematological research of the highest scientific quality and clinical relevance. Additionally, educational material, reviews on basic developments, editorial short notes, images in hematology, and letters from hematology specialists and clinicians covering their experience and comments on hematology and related medical fields as well as social subjects are published. As of December 2015, The Turkish Journal of Hematology does not accept case reports. Important new findings or data about interesting hematological cases may be submitted as a brief report.