Hemoglobin最新文献

{"title":"Prevalence and Molecular Characteristics of Hemoglobin Variants in Laibin City, Central Guangxi of Southern China.","authors":"Yuan-Yuan Huang, Li-Hua Ye, Wei Li, Gui-Xi Wei, Xue-Chun Qin, Hui-Ping Wen, Qing-Yan Zhong, Li-Zhu Chen, De-Jian Yuan","doi":"10.1080/03630269.2025.2477586","DOIUrl":"https://doi.org/10.1080/03630269.2025.2477586","url":null,"abstract":"<p><p>This study investigated hemoglobin (Hb) variant prevalence and molecular characteristics in Laibin City, Central Guangxi, China. Using capillary electrophoresis (CE), 33,958 individuals from six regions within Laibin area were screened, with hematological parameters analyzed via automated cell counters. Gap-PCR/RDB-PCR identified common α/β-thalassemia mutations, while Sanger sequencing characterized Hb variants. Single-molecule real-time (SMRT) sequencing was performed to identify breakpoints in a sample with a large duplication and to detect multiple mutations in another sample. Multiple ligation-dependent probe amplification (MLPA) was used for duplication validation. Among 231 Hb variant carriers (0.68% prevalence), 18 mutation types were identified: 7 α-chain, 6 β-chain, and 5 δ-chain variants. Hb New York was most frequent (30.3%, 70/231), followed by Hb E (27.3%, 63/231) and Hb Q-Thailand (20.8%, 48/231). Two novel variants-Hb Laibin (<i>HBA2</i>: c.44T>C) and Hb Anti-Lepore Laibin-were discovered, alongside China's first reported Hb Matsue-Oki case. In conclusion, we observed a high carrying rate of Hb variants in Laibin City. Our findings contribute to the increasing number and diverse heterogeneity of Hb variants in Central Guangxi, which should be useful for genetic counseling and the prevention of hemoglobinopathies. The flexible application of a diverse array of molecular detection techniques is essential to avoid missed diagnoses and achieve high diagnostic efficiency.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-9"},"PeriodicalIF":1.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual Causes of β Thalassemia Trait: Discovery of another Three Novel <i>SUPT5H</i> Variants.","authors":"Nik Fatma Fairuz Nik Mohd Hasan, Ahlem Achour, Tamara Koopmann, Adriaan van Gammeren, Joep van der Leeuw, Huib Ceelie, Daniel Stieber, Frank Baas, Cornelis L Harteveld","doi":"10.1080/03630269.2025.2484230","DOIUrl":"https://doi.org/10.1080/03630269.2025.2484230","url":null,"abstract":"<p><p>Beta (β) thalassemia is an inherited disorder that occurs following mutations or deletions in the β globin gene. Rarely, it is caused by variants in genes coding for erythroid transcriptional factors or trans-acting factors. Here, we report three novel variants of <i>SUPT5H</i> revealed by next generation sequencing. This, gene has been progressively acknowledged as a mimicker of β thalassemia trait in two independent individuals and one family. These individuals have the same features, including hypochromic microcytic indices, increased Hb A₂ levels, without mutations in the β globin gene. The three novel <i>SUPT5H</i> variants identified in this study (c.1168_1169del, c.2688del and c.307+1G>A) are frameshift variants leading to a premature stop codon or an intronic variant predicted to alter the splice site consensus sequence by <i>in silico</i> software. All three variants are characterized as Loss-of-Function variants either by generating a truncated protein or haplo-insufficiency due to nonsense-mediated decay. These findings confirm the general observation that most variants in <i>SUPT5H</i> associated with a β thalassemia trait phenotype are Loss-of-Function variants. This gene should be considered as a potential target gene in the genetic diagnosis of any unsolved cases of increased HbA₂ and unexplained inconsistency of phenotype and genotype of β thalassemia intermedia.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Characterization of Complex Thalassemia with Multiple Variants in β-Globin Gene Cluster and the Identification of a Novel Structural Rearrangement in γ-Globin Gene.","authors":"Yonghua Xu, Haiyan Luo, Ting Huang, Yuan Fang, Pengpeng Ma, Yan Yang, Junhui Shao, Yongyi Zou, Yanqiu Liu, Jihui Zhou, Bicheng Yang","doi":"10.1080/03630269.2025.2484236","DOIUrl":"https://doi.org/10.1080/03630269.2025.2484236","url":null,"abstract":"<p><p>Molecular characterization was performed for investigation of β-globin gene cluster in a pregnant Chinese female with mild microcytic hypochromic anemia accompanied with complicated hemoglobin fractions. Routine hematological parameters and hemoglobin analyses were conducted using an automated cell counter and capillary electrophoresis, separately. Long-read single molecule real time (SMRT) sequencing was employed to molecularly characterize this individual. Hematological indices showed mild microcytic hypochromic anemia, and hemoglobin analyses demonstrated normal HbA2 percentage of 2.3% and increased HbF value of 13.1% in this female. SMRT thalassemia genetic testing showed a heterozygous β⁺ mutation <i>HBB</i>:c0.316-197C > T (β^{IVS-II-654 (C>T)}) and heterozygous <i>HBG2:</i>c.-211C > T (-158Gγ (C > T)), which has independently been reported to result in elevated HbF levels. A variant <i>HBD</i>: c.-127T > C (-77 (T > C)) was also identified in the promoter region, which has been frequently reported to result in normal HbA2 levels in patients with β-thalassemia. All the three variants were further validated by Sanger sequencing. Moreover, SMRT analysis unraveled a novel duplicated structural variation of <i>HBG1</i>/<i>HBG2</i> (^Gγ^Aγ/^{-158(C>T)GγGγGγAγ}), a rearrangement of four γ-globin genes including one entire <i>HBG1</i> and three entire <i>HBG2</i> in one chromosome. We herein first described a novel structural quadruplet γ-globin genes of <i>HBG2</i> by SMRT and reported the molecular characterization of a complex thalassemia with variants involving <i>HBG1</i>/<i>HBG2</i>, <i>HBD</i> and <i>HBB</i> genes. Our work may facilitate genetic counseling and bring insight into future diagnosis of complex thalassemia.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid and Visual Molecular Detection of High Hb F Determinants; HPFH6, Asian Indian inv-del (^Aγδβ)⁰-Thalassemia, and Thai del-inv-ins (^Aγδβ)⁰-Thalassemia Using LAMP Colorimetric Phenol Red Assays.","authors":"Wittaya Jomoui, Wanicha Tepakhan","doi":"10.1080/03630269.2025.2477614","DOIUrl":"https://doi.org/10.1080/03630269.2025.2477614","url":null,"abstract":"<p><p>Hemoglobin (Hb) F, or fetal hemoglobin, is the predominant Hb in fetuses and is converted to adult hemoglobin (Hb A) at the age of 2 years. However, high Hb F levels in adults are typically present in conditions such as β-thalassemia disease and high Hb F determinants including large deletional β-globin gene clusters, and hereditary persistence of fetal hemoglobin (HPFH). The accurate detection of these conditions is crucial for effective disease management and genetic counseling. Several molecular techniques have been used to identify high Hb F determinants but require advanced instrumentation, highly skilled personnel, high cost, long time duration, and post-PCR processing. This study aimed to develop a rapid and cost-effective molecular assay for detecting common high Hb F determinants using colorimetric loop-mediated isothermal amplification (LAMP) with phenol red assays. We focused on the detection of HPFH6, Asian Indian inv-del (^Aγδβ)⁰-thalassemia, and Thai del-inv-ins (^Aγδβ)⁰-thalassemia. A total of 331 DNA samples encompassing 21 genotypes were screened using the developed LAMP assays, which were optimized to detect these determinants within 60-70 min. The assays showed high sensitivity (100%) and specificity (99.6-100%) in each mutation with detection limits of 2.5 ng/reaction. Validation by comparison with conventional methods confirmed the efficacy of the LAMP assays, which is simple, inexpensive, and suitable for use in low-resource settings. Rapid performance, visual detection, and accurate diagnosis may be useful for genetic counseling, particularly in Thailand and Southeast Asia. This innovation is suitable for application in thalassemia screening programs, especially in remote areas.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-8"},"PeriodicalIF":1.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alloimmunization in β-Thalassemia and Sickle Cell Disease in Middle Eastern Countries: A Systemic Review.","authors":"Nasir Al-Allawi, Muqdad Mn Al-Mousawi, Sarah Al Allawi, Kevi J Ibrahim","doi":"10.1080/03630269.2025.2471923","DOIUrl":"https://doi.org/10.1080/03630269.2025.2471923","url":null,"abstract":"<p><p>Sickle cell disease and β-thalassemia are important health problems in Middle Eastern countries. Transfusion is the cornerstone of the management in these disorders, and red blood cell alloimmunization is among the well-recognized adverse effects associated with it. We reviewed the literature on published studies on alloimmunization prevalence, its associated risk factors, and transfusion policies employed in these countries. Our review included 39 studies on thalassemia (including 9005 patients), and 19 on sickle cell disease (including 3867 patients). The mean alloimmunization prevalence rate in thalassemia was 13.0% (95% CI: 10.0-15.0%), while that in sickle cell disease was 14.0% (95% CI: 10.0 - 19.0%). The distribution of the prevalence rates showed considerable heterogeneity in both diseases. The most frequent alloantibodies detected were anti-K (25.9%), Anti-E (21.8%), and Anti-D (9.2%), with Rhesus and K antibodies comprising 74.2% of all antibodies detected. Some risk factors were significant in several studies, including older age, female sex, older age at first transfusion, number of transfused units, and splenectomy. The prevalence of alloimmunization was significantly higher in retrospective studies compared to cross-sectional ones, in both thalassemia and sickle cell disease (<i>P</i> = 0.04 in each). This review reaffirmed the need to provide ABO+Rhesus + K matched blood to hemoglobinopathy patients in the Middle East, and the need for more research on Rhesus variants in this part of the world.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-15"},"PeriodicalIF":1.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term and Transient Calcium Channel Blockers; A Systematic Review of Their Role in the Management of Cardiomyopathy in Transfusion-Dependent Thalassemia.","authors":"Ali Bazi, Alireza Khanahmad, Mohammad Hossein Khazaee-Nasirabadi, Mohammad Pirouzbakht, Kobra Ghorbani Biregani, Fatemeh Peymaninezhad, Roohollah Mirzaee Khalilabadi","doi":"10.1080/03630269.2025.2470718","DOIUrl":"https://doi.org/10.1080/03630269.2025.2470718","url":null,"abstract":"<p><p>Calcium channel blockers (CCBs) for long-term (L) and transient (T) calcium channels (LTCC and TTCC) on cardiomyocytes have been suggested to manage iron-induced cardiomyopathy in transfusion-dependent thalassemia patients. However, the results of clinical trials on the effectiveness of CCBs have been conflicting. Here, we systematically reviewed previous studies to investigate the potential factors that could act as therapeutic modifiers and explain these discrepancies. This systematic review was conducted employing the PRISMA guideline to retrieve clinical trials and animal studies investigating the efficacy of CCBs. Studies in the following databases were collected: Web of Science, PubMed, Scopus, Google Scholar, Clinical Trials, Iranian Registry for Clinical Trials, and Cochrane CENTRAL. Keywords included the trade and generic names of various CCBs, thalassemia, and cardiomyopathy. Our Primary search resulted in 297 studies, of which 21 (n = 7 trials and n = 14 animal studies) were further analyzed. The most important parameters that could potentially influence the clinical effectiveness of CCBs in managing iron-induced cardiomyopathy included baseline cardiac iron content, diversity of iron entry routes (LTCCs, TTCCs, DMT-1, etc.), type of CCBs used, iron-induced irreversible functional/structural cardiac changes, iron-Ca²⁺ joint metabolic dysregulation, deregulated expression of LTCCs and TTCCs, interaction of CCBs with iron chelators, disease-related complications, interactions of CCBs with various supplements used by patients, vitamin D and other nutrient deficiencies, and duration of treatment with CCBs. These items should be considered in future trials to draw more robust conclusions about the effectiveness of CCBs in preventing cardiac iron deposition and associated cardiomyopathy in TDT patients.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-15"},"PeriodicalIF":1.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haplotype-Specific Genetic Epidemiology of Sickle Cell Anemia Patients in Accra, Ghana: Patterns, Clinical Implications, and Public Health Responses.","authors":"Francis Abeku Ussher, Edwin Ferguson Laing, Ernest Kissi Kontor, Alex Bismark Atta-Owusu, Nityanand Jain, Robert Amadu Ngala, Shadrach Coffie Asiedu","doi":"10.1080/03630269.2025.2474609","DOIUrl":"https://doi.org/10.1080/03630269.2025.2474609","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a genetic disorder with a diverse spectrum of clinical presentation, often determined by inherited β^S gene haplotypes. Ghana, a country with a significant SCD burden, lacks population haplotype frequency data, hindering anthropological, genetic, and clinical understanding and management of the disease. A prospective sample of 191 SCD patients (sickle cell anemia; homozygous HbSS) was recruited at the Korle-Bu Teaching Hospital, Accra. Identification of β^S gene haplotypes was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Hematological tests were performed using routine laboratory procedures. Kruskal-Wallis ANOVA with Dunn post-hoc was used to compare the hematological parameters. Multinomial probability models were used to compare the frequencies of the observed haplotypes with those reported in other African countries. The Atypical haplotype was disproportionately prevalent (58%), followed by the Bantu/CAR (20%) and Benin (10%) haplotypes. Significant differences were observed between the haplotypes in lymphocyte count, platelet count, sodium and potassium levels (<i>P</i> < 0.001). In addition, disease severity varied significantly between haplotypes (<i>P</i> = 0.010), with notable differences between the Atypical and Bantu/CAR haplotypes (<i>P</i>_FDR = 0.020). Multinomial probability testing revealed a substantial deviation from the expected haplotype distribution, highlighting significant differences in haplotype frequencies between Ghana and other African countries. The Wright-Fisher model showed that the variation in Arab-Indian haplotype frequency reached zero by the 100^th generation. Our findings highlight the need to study haplotype composition in Ghana to identify population-specific risk factors and tailor public health interventions to better manage patient needs.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-9"},"PeriodicalIF":1.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Health-Related Quality of Life in Thalassemia: Low-Dose Thalidomide vs. Standard Care-Insights from a Comparative Study.","authors":"Varsha Mishra, Pratibha Singh Yadav, Reema Singh, Sujay Rainchwar, Roy J Palatty, Tribikram Panda, Karuna Jha, Rohan Halder, Narendra Agrawal, Dinesh Bhurani","doi":"10.1080/03630269.2025.2473526","DOIUrl":"https://doi.org/10.1080/03630269.2025.2473526","url":null,"abstract":"<p><p>Thalassemia is a hemoglobinopathy that affects many people worldwide. Although treatments such as iron chelation and safe transfusions have improved life expectancy, patients still experience complications. Thalidomide, with its immunomodulatory and anti-angiogenic properties, has been found to increase the expression of the γ-globin gene and promote erythroid cell proliferation. Our study compared thalidomide-treated and standard therapy groups, assessing health-related quality of life in thalassemia patients using the SF-36 questionnaire tailored for the Indian population. A total of 84 patients (Thalidomide: 50, Standard: 34) were enrolled. Sixty-four percent of patients on thalidomide became transfusion-free within 4-6 months. The mean duration of transfusion requirement in the thalidomide group increased from 20 to 35 days in 30% of patients. Patients aged ≤ 20 years, without splenectomy, and unemployed had significantly better physical health component (PHC) scores with thalidomide therapy compared to standard therapy (<i>P</i> = 0.027, <i>P</i> = 0.0007, and <i>P</i> = 0.045, respectively). On the other hand, patients aged >20 years and with intact spleen had significantly better mental health component (MHC) scores with thalidomide therapy compared to standard therapy (<i>P</i> = 0.006 and <i>P</i> < 0.00001, respectively). Thalidomide therapy showed significantly better MHC scores than standard therapy on all four scales. Thalidomide therapy shows significant promise in improving the HRQoL for thalassemia patients, particularly in those with early initiation, as indicated by enhanced physical and mental health component scores and improved vitality, emotional well-being, role-emotional, and social functioning compared to standard care.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-7"},"PeriodicalIF":1.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Associated Factors of Zinc and Vitamin D Deficiencies in Pediatric and Young Adult Patients with Non-Transfusion-Dependent Thalassemia.","authors":"Poonyapon Rodchaprom, Kanda Fanhchaksai, Supawadee Maneekesorn, Kulnipa Kittisakmontri, Pimlak Charoenkwan","doi":"10.1080/03630269.2025.2471927","DOIUrl":"https://doi.org/10.1080/03630269.2025.2471927","url":null,"abstract":"<p><p>Micronutrient deficiencies pose significant long-term risks in non-transfusion dependent thalassemia (NTDT) patients. Zinc deficiency can impair growth, cause atopic dermatitis, and increase susceptibility to respiratory infections, while vitamin D deficiency disrupts bone mineralization and metabolism. This study aimed to determine the prevalence of zinc and vitamin D deficiencies and investigate associated factors in pediatric to young adult NTDT patients. A cross-sectional study was conducted at Chiang Mai University Hospital, enrolling NTDT patients aged 5 to 25 years who received fewer than three transfusions annually. Serum zinc and vitamin D levels were measured. Patients and parents completed a 3-day food diary and a sun exposure questionnaire. Zinc deficiency was defined as levels below the reference level for age. Vitamin D deficiency was defined as levels <20 ng/mL. Clinical and hematologic parameters were compared between groups with and without deficiencies. Forty-five patients with NTDT were enrolled, including 23 males (51.1%) males, with a mean age of 12.8 ± 5.3 years. Zinc deficiency affected 13 patients (28.9%), while 23 patients (51.1%) had vitamin D deficiency. Thinness was observed more frequently in patients with zinc deficiency. However, this finding did not reach statistical significance. Older age and inadequate sun exposure were associated with vitamin D deficiency. This study underscores a high prevalence of zinc and vitamin D deficiencies in pediatric and young adult NTDT patients and identifies the associated factors. Addressing and monitoring these deficiencies are crucial for optimizing long-term health outcomes in this patient group.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Single Nucleotide Polymorphisms on Clinical Phenotypes of Sabahan Transfusion-Dependent β-Thalassemia Patients with Homozygous Filipino β⁰-Deletion.","authors":"Latifah Suali, Falah Abass Mohammad Salih, Mohammad Yusof Ibrahim, Mohammad Saffree Bin Jeffree, Emma Suali, Fong Siew Moy, Yap Shook Fe, Caroline Sunggip","doi":"10.1080/03630269.2024.2448175","DOIUrl":"10.1080/03630269.2024.2448175","url":null,"abstract":"<p><p>Sabah has the highest prevalence of β-thalassemia in Malaysia, with the Filipino β⁰-deletion as the predominant mutation. Patients with the homozygous Filipino β⁰-deletion exhibit phenotypic heterogeneity due to various genetic modifiers, yet the effects of these modifiers on the clinical phenotype remain poorly understood. This study investigated the effects of the coinheritance of α-thalassemia, <i>Xmn</i>I-^Gγ rs7482144, <i>BCL11A</i> rs766432, and 5'HS4 rs16912979 polymorphisms on the clinical phenotype of homozygous Filipino β⁰-deletion patients in Sabah. Molecular analyses were performed on 124 homozygous Filipino β⁰-deletion patients using gap-PCR, PCR-RFLP, multiplex PCR, ARMS-PCR, gel electrophoresis, and DNA sequencing. Data showed that the coinheritance of the -α^3.7 deletion significantly affected the clinical phenotypes of homozygous Filipino β⁰-deletion patients (<i>p</i> < 0.05). Patients with the -α^3.7/-α^3.7 genotype (5.6%) had a less severe clinical phenotype compared to those with the αα/αα (71.8%) and -α^3.7/αα (22.6%) genotypes. Our data further revealed that the MAFs of the X<i>mn</i>I-^Gγ rs7482144 and <i>BCL11A</i> rs766432 polymorphisms in these patients were 0.032 and 0.194, respectively. Interestingly, none of these single nucleotide polymorphisms significantly influenced the clinical phenotype of the patients. The effect of the 5'HS4 rs16912979 polymorphism on the clinical phenotype could not be assessed due to its rarity (1.6%). However, a novel 5'HS4 c.733+G mutation was identified, warranting further investigation of its potential impact on β-thalassemia pathogenesis. Our findings indicate that the clinical phenotype of patients with the homozygous Filipino β⁰-deletion is strongly influenced by the coinheritance of the -α^3.7 deletion, but not by the <i>Xmn</i>I-^Gγ rs7482144 and <i>BCL11A</i> rs766432 polymorphisms.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"10-19"},"PeriodicalIF":1.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}