Hemoglobin最新文献

{"title":"A Rare Alpha-Globin Mutation: Detailed Analysis of the Hb Rogliano Variant (α1 Cod 108 Thr→Asn).","authors":"Alifia Nur Hidayah, Indra Lesmana, Tri Ratnaningsih, Nur Imma Fatimah Harahap, Nafis Muhimmatul 'Ulya, Vincentius Sw Budhyanto, Niken Satuti Nur Handayani","doi":"10.1080/03630269.2026.2715749","DOIUrl":"https://doi.org/10.1080/03630269.2026.2715749","url":null,"abstract":"<p><p>α-Thalassemia is an autosomal recessive disorder characterized by reduced synthesis of α-globin chains, most commonly due to deletions within the α-globin gene cluster. Non-deletional variants are less common and contribute to the molecular heterogeneity of the disease. Advances in long-read sequencing have improved the analysis of complex genomic regions, including highly homologous genes such as <i>HBA1</i> and <i>HBA2</i>. Targeted long-range PCR amplification of the <i>HBA1</i> and <i>HBA2</i> genes was followed by long-read sequencing on the PromethION 24 platform (Oxford Nanopore Technologies). Subsequently, the sequencing data were analyzed and visualized using the Integrative Genomics Viewer (IGV). Long-read sequencing achieved an average depth of >390x across all target regions, enabling reliable variant detection. This analysis identified five variants in the <i>HBA1</i> and <i>HBA2</i> genes, namely <i>HBA1</i>:c.326C > A (p.Thr108Asn; Hb Rogliano), <i>HBA1</i>:c.-41C > G, <i>HBA2</i>:c0.300 + 55T > G, <i>HBA2</i>:c0.301-24delinsCTCGGCCC, and <i>HBA2</i>:c.-41C > G. Based on ClinVar classification, <i>HBA1</i>:c.326C > A (p.Thr108Asn) was categorized as likely pathogenic, while the remaining variants were classified as benign or likely benign. To our knowledge, this is the first report of Hb Rogliano in Indonesia and highlights the utility of long-read sequencing for the molecular characterization of rare α-globin variants.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-6"},"PeriodicalIF":1.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766127","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":"Screening for the 'Silent' Burden of Menstrual and Mental Health Among Women with Sickle Cell Disease: A Prospective Study.","authors":"Zachary Ramsay, Nicki Chin, Deva Sharma, Margaret Wisdom-Phipps, Leroy Campbell, Jennifer Knight-Madden, Monika Asnani","doi":"10.1080/03630269.2026.2715007","DOIUrl":"10.1080/03630269.2026.2715007","url":null,"abstract":"<p><p>This study screened for major depression and generalized anxiety disorder (GAD) across the menstrual cycle among women with sickle cell disease (SCD) and examined associations with heavy menstrual bleeding (HMB), dysmenorrhea, and sex hormones. A total of 125 Jamaican women aged 18 and over with SCD, regular menses, and no recent hormonal contraceptive use completed follicular- and luteal-phase visits including serum estradiol and progesterone measurements and validated mental and menstrual health and quality-of-life questionnaires. Higher Menstrual Symptom Questionnaire and Menstrual Bleeding Questionnaire scores reflect more severe menstrual pain and menstrual heaviness, respectively, including quality-of-life impact. Menstrual scores were standardized as z-scores and odds ratios represent the change in odds per one-standard deviation change from the sample mean. Major depression and GAD were screened using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Screen-positive rates for major depression and GAD were 44.8% and 39.2% with no differences between phases; and 32% reported passive self-harm ideations. Marginal mean scores were HMB 11.6 ± 4.9 (scale: 0-24) and dysmenorrhea 62.9 ± 13.5 (scale: 24-120). Worse dysmenorrhea was associated with higher odds of major depression risk (odds ratio, OR = 2.6), whereas better quality-of-life in pain (OR = 0.9) and sleep (OR = 0.8) were associated with lower odds. Severe genotypes (OR = 0.1) and better quality-of-life in stiffness (OR = 0.9) and sleep (OR = 0.9) were associated with lower odds of GAD risk. Estradiol, progesterone, and HMB showed no significant adjusted effects. The high prevalence of GAD and major depression risk, and the association between depression and dysmenorrhea suggest that routine screening is needed in this vulnerable group.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-14"},"PeriodicalIF":1.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705745","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":"Hydroxyurea and Gut Microbiome Interactions in Sickle Cell Disease: Toward Adjunctive Microbiome-based Therapy.","authors":"Bipasha Banerjee, Tuphan Kanti Dolai, Kaustav Ghosh","doi":"10.1080/03630269.2026.2702342","DOIUrl":"10.1080/03630269.2026.2702342","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a monogenic disorder marked by hemoglobin S polymerization, resulting in chronic hemolysis, vaso-occlusion, systemic inflammation, and progressive multiorgan damage. Despite major therapeutic advances, SCD remains a complex inflammatory condition with significant morbidity. Hydroxyurea is the cornerstone of treatment, primarily by inducing fetal hemoglobin and reducing vaso-occlusive crises and hemolysis. It also exerts anti-inflammatory effects by decreasing leukocyte activation and endothelial adhesion. However, hydroxyurea does not fully reverse microvascular injury, persistent immune activation, or organ dysfunction, particularly renal and endothelial damage. This review aims to synthesize current evidence on the interactions between hydroxyurea and the gut microbiome in SCD and to evaluate the potential role of microbiome-directed therapies as adjunctive strategies to control inflammation and organ damage. Recent evidence highlights the gut microbiome as a critical regulator of immune homeostasis and inflammation in SCD. Dysbiosis, marked by reduced microbial diversity and diminished short-chain fatty acid (SCFA) production, drives cytokine activation, endothelial dysfunction, and pain sensitization. Emerging studies suggest that hydroxyurea may partially restore microbial balance, yet residual dysbiosis persists. Microbiome-directed therapies, including probiotics and microbial metabolites, show promise for reducing pro-inflammatory cytokines, strengthening gut barrier integrity, and modulating immune responses. Probiotic strains such as <i>Lactobacillus</i> and <i>Bifidobacterium</i>, together with SCFA-mediated pathways, may enhance anti-inflammatory effects and address therapeutic gaps left by hydroxyurea. A combined strategy targeting both hematologic and microbiome pathways may offer superior control of inflammation and organ damage. Integrating microbiome-based interventions with conventional therapy represents a promising, patient-centered approach to improving long-term outcomes and quality of life in SCD.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"321-331"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520261","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 Epidemiology of δβ-Thalassemia and Hereditary Persistence of Fetal Hemoglobin (HPFH) in the Quanzhou Childbearing-Age Population, China.","authors":"Qianmei Zhuang, Xiaolong Liu, Meizhen Yan, Chunqiang Liu, Geng Wang, Yuying Jiang","doi":"10.1080/03630269.2026.2692950","DOIUrl":"10.1080/03630269.2026.2692950","url":null,"abstract":"<p><p>δβ-Thalassemia and hereditary persistence of fetal hemoglobin (HPFH) are uncommon hemoglobinopathies. This study aimed to define the molecular epidemiological features of δβ-thalassemia and HPFH in the childbearing-age population of Quanzhou, China, to inform precise prevention strategies and genetic counseling. From a free pre-pregnancy thalassemia screening cohort (n = 19,154), 92 individuals with elevated HbF (≥2%) and 11 control groups with normal HbF (≤2%) were included. DNA analysis of common deletion-type δβ-thalassemia/HPFH mutations (SEA-HPFH, Chinese type Gγ+(Aγδβ)⁰, Taiwan type β⁰) and non-deletion-type HPFH mutations was performed by gap-PCR, PCR-reverse dot hybridization, and Sanger sequencing. The correlation between hematological parameters and genotypes was also analyzed. The results suggest that the detection rate of deletion-type HPFH/δβ-thalassemia was 0.063% (12/19154), mainly SEA-HPFH and Chinese Gγ+(Aγδβ)⁰. The detection rate of γ-globin gene mutations and non-deletion-type HPFH was 0.329% (63/19154). 9 different γ-globin promoter mutations were identified. The most frequently detected variants were <i>HBG2</i>:c.-211C>T, <i>HBG1</i>:c.-29G>A, and <i>HBG1</i>:c.-272_-275dupAGCA. However, based on functional relevance, three key variants were highlighted: <i>HBG1</i>:c.-211C>T, <i>HBG1</i>:c.-249C>T, and the novel <i>HBG2</i>:c.-253_-254dup. The remaining variants (<i>HBG1</i>:c.-29G>A, <i>HBG1</i>:c.-272_-275dupAGCA, <i>HBG1</i>:c.-404A>G, <i>HBG1</i>:c.-417G>C, <i>HBG1</i>:c.-420C>A) are described as benign polymorphisms or variants in strong linkage disequilibrium with <i>HBG2</i>:c.-211C>T. Deletion-type δβ-thalassemia/HPFH is rare in Quanzhou. SEA-HPFH and Chinese Gγ+(Aγδβ)⁰ are more common. Non-deletion-type HPFH, especially the double heterozygous state <i>HBG1</i>:c.-29G>A/<i>HBG2</i>:c.-211C>T, is significantly more common. These findings reveal the unique molecular epidemiological characteristics of δβ-thalassemia and HPFH in this region, providing important data for genetic counseling and prenatal diagnosis.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"343-350"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436699","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":"Compound Heterozygous Hemoglobin Minneapolis-Laos and Codon 41/42 (-TTCT) in a Thai Female Adult: A Case Report and Literature Review.","authors":"Sitanun Preechathaveekid, Tarinee Rungjirajittranon, Nuttiruetai Chanpo, Boonyanuch Dujjawan, Chattree Hantaweepant","doi":"10.1080/03630269.2026.2684611","DOIUrl":"10.1080/03630269.2026.2684611","url":null,"abstract":"<p><p>Thalassemia is a prevalent genetic disorder in Southeast Asia. The Hemoglobin Minneapolis-Laos variant is very rarely reported with only two previously published reports that profile a total of three patients. Here, we present the first reported case of compound heterozygous β zero (β⁰)-thalassemia and Hemoglobin Minneapolis-Laos in a 46-year-old Thai female. She presented at Siriraj Hospital (Bangkok, Thailand) with chronic microcytic anemia, which is a more severe phenotype than would be expected from either trait alone. Initial hemoglobin electrophoresis via high-performance liquid chromatography and capillary electrophoresis revealed elevated hemoglobin A₂ (5.5% and 6.3%, respectively), which is a finding consistent with a β-thalassemia trait, but this finding failed to explain the full extent of her anemia. Next-generation sequencing was then performed to investigate for a congenital red blood cell disorder. The results identified the following two mutations in the β-globin gene (<i>HBB</i>): heterozygous β⁰-thalassemia codon 41/42 (-TTCT), and <i>HBB</i> c.356T >A, the latter of which is consistent with hemoglobin Minneapolis-Laos. This case highlights the importance of advanced genetic testing to diagnose rare hemoglobin variants that cannot be identified by conventional investigation and further contributes to our understanding of this rare combination's clinical phenotype.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"363-369"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217061","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":"Compound Heterozygosity for Hb Port Phillip and the -α^3.7 Deletion Leads to Persistent Hypoxemia in a Chinese Pediatric Family.","authors":"Hualei Luo, Zhenmin Ren, Yuhua Ye, Tao Wu, Xiaoying Fu, Nan Cheng, Jiehua Chen, Yunsheng Chen","doi":"10.1080/03630269.2026.2676643","DOIUrl":"10.1080/03630269.2026.2676643","url":null,"abstract":"<p><p>Hemoglobin variants and α-thalassemia deletions are uncommon causes of unexplained hypoxemia in children. This study reports a Chinese family affected by compound heterozygous <i>HBA₂</i> mutations that decrease hemoglobin-oxygen affinity. Clinical data, oxygen saturation (SpO₂) trends, chest imaging, capillary hemoglobin electrophoresis, and genetic testing were conducted on the proband and his family members. The proband had persistently low SpO₂ after pneumonia resolution, without respiratory distress; his 4-year-old brother experienced similar hypoxemia with normal cardiopulmonary evaluations. Capillary electrophoresis showed increased variant hemoglobin fractions in both siblings and their mother. Genetic analysis revealed compound heterozygosity: a maternally inherited <i>HBA₂:</i> c.275T > C (p.L92P, Hb Port Phillip) and a paternally inherited -α^3.7 deletion. The proband's mother is heterozygous for the point mutation and asymptomatic, while the father carries the -α^3.7 deletion. This is the first report of a compound heterozygote for Hb Port Phillip and -α^3.7 deletion with hypoxemia in a Chinese family, thus broadening the phenotype-genotype spectrum of hemoglobinopathies. The unexpected low oxygen saturation may result from a hemoglobin variant in the setting of mild microcytic anemia; hemoglobin electrophoresis and genetic testing are crucial for accurate diagnosis and can prevent unnecessary interventions.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"387-394"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669365","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":"Expression Differences of Abnormal Hemoglobin New York in Infants, Children and Adults, and Analysis of Clinical Phenotypes and Genotypes in Combination with Thalassemia.","authors":"Guang-Kuan Zeng, Yun-Hong Yao, Li-Ye Yang, Yi-Yuan Ge","doi":"10.1080/03630269.2026.2702340","DOIUrl":"10.1080/03630269.2026.2702340","url":null,"abstract":"<p><p>The study investigated expression differences of Hb New York (<i>HBB</i>:c.341T > A) across infants, children, and adults, and analyzed the clinical phenotypes and genotypes when co‑inherited with thalassemia. We retrospectively reviewed 317 cases of Hb New York carriers, assessing hematological parameters, hemoglobin electrophoresis, and genetic testing results. All samples carried the <i>HBB</i>:c.341T > A mutation, including 266 heterozygotes (192 adults, 74 infants and children) and 51 compound heterozygotes with thalassemia. Adult heterozygotes exhibited normal hematological phenotypes, with Hb New York levels of 43.6 ± 2.9%. Compound heterozygosity with α-thalassemia silent carrier showed normal or near-normal red blood cell parameters (Hb New York: 38.8 ± 2.9%), whereas co-inheritance with α-thalassemia trait caused microcytosis, hypochromia, and mild anemia (Hb New York: 35.2 ± 2.4%). Co-inheritance with β-thalassemia mutations (β^CD17, β^CD71-72, <i>HBB</i>:c.91A > G) presented mild β-thalassemia traits (Hb New York > 91.6%), and combination with Hb J-Bangkok showed normal phenotypes. The Hb New York level in newborns gradually increased over the months. The content of Hb New York in heterozygotes was 4.8 ± 2.0%, and when combined with thalassemia gene mutations, it was 5.1 ± 2.3%, indicating similar Hb New York levels between the two groups. We conclude that Hb New York levels are positively correlated with normal α-globin chain expression but inversely correlated with normal β-globin chain expression. Hb New York heterozygotes have normal hematological phenotype; compound heterozygosity with an α-thalassemia silent carrier causes minimal hematological alterations, whereas combination with other thalassemias induces anemia of variable severity dependenting on the thalassemia subtype.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"351-359"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602386","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":"Successful Management of Transfusion-Dependent Unstable Hemoglobin Perth with Splenectomy: First Report from Iran and Literature Review.","authors":"Samin Alavi, Hossein Najmabadi, Mehdi Sarafi, Asghar Ramyar","doi":"10.1080/03630269.2026.2652612","DOIUrl":"10.1080/03630269.2026.2652612","url":null,"abstract":"<p><p>Unstable hemoglobin (Hb) variants are a rare cause of congenital non-spherocytic hemolytic anemia, characterized by hemoglobin instability and Heinz body formation. Diagnosis is often challenging and requires a high index of suspicion, supported by targeted laboratory investigations. We report the first documented case of an unstable hemoglobin variant identified as hemoglobin Perth (also known as Hb Abraham Lincoln) from Iran in a patient who was transfusion-dependent since early childhood. At 10 years of age, he presented with acute cholecystitis and cholelithiasis, accompanied by profound direct hyperbilirubinemia. He underwent cholecystectomy and splenectomy, which resulted in significant clinical improvement, including transfusion independence and stabilization of hemoglobin levels. This case is particularly noteworthy for the exceptionally high levels of direct bilirubin unreported in previous cases of Hb Perth, as well as the successful therapeutic outcome achieved following splenectomy.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"381-386"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204750","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":"Unstable Hemoglobin Variants: Molecular Mechanisms, Clinical Phenotypes, and a Practical Diagnostic and Management Approach.","authors":"Aikaterini Poulaki, Sophia Delicou","doi":"10.1080/03630269.2026.2674946","DOIUrl":"10.1080/03630269.2026.2674946","url":null,"abstract":"<p><p>Unstable hemoglobin variants are rare structural hemoglobin disorders in which alterations in the globin chain reduce hemoglobin stability, promoting denaturation, precipitation, and red cell injury. Affected individuals may present with a broad spectrum, ranging from compensated hemolysis to severe transfusion-dependent anemia, and episodes are commonly exacerbated by intercurrent illness or oxidative stress. Diagnosis remains challenging because many unstable variants are not readily recognized by routine hemoglobin separation, and classic morphological clues (Heinz bodies; bite/blister cells) are neither uniformly present nor specific. This review summarizes the molecular mechanisms underlying hemoglobin instability, outlines phenotypic patterns across the lifespan (including neonatal-limited instability involving fetal hemoglobin), and provides a practical diagnostic framework that integrates hemoglobin separation methods, stability assays, and molecular testing. Supportive care, including avoidance of oxidant triggers, folate supplementation, and transfusion support when needed, remains the mainstay, while splenectomy and curative transplantation are reserved for selected severe cases.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"299-307"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015270","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":"Genotypic Characterization of Hemoglobinopathies in Azerbaijan: A Review of 10 Years at a Referral Center.","authors":"Agharza Aghayev, Khuraman Jafarova, Zenfira Mirzeyeva, Seher Ismayilova, Tahira Mammadova, Valeh Huseynov, Zehra Oya Uyguner","doi":"10.1080/03630269.2026.2680937","DOIUrl":"10.1080/03630269.2026.2680937","url":null,"abstract":"<p><p>Hemoglobinopathies constitute a major cause of hereditary anemia and remain a significant public health challenge in Azerbaijan. The purpose of this study was to delineate the variant spectrum and genotype distribution in a large national cohort and to evaluate the contribution of next-generation sequencing (NGS) to molecular diagnosis. During the study period, 1,000 unrelated individuals with suspected hemoglobinopathies underwent hematological and molecular genetic evaluation at a national referral center in Azerbaijan. Overall, 777 of 1,000 (77.7%) individuals were genetically positive. Of these, β-thalassemia was most frequent (59.9%, 466/777), followed by α-thalassemia (22.0%, 171/777) and co-inheritance of α/β-thalassemia (9.52%, 74/777). In addition, HbS-related genotypes were detected in 6.2% (48/777) and other rare hemoglobin variants in 1.3% (10/777). In α-thalassemia, the most common genotypes were αα/-α³·⁷ (22.81%), -α³·⁷/-^20.5 (17.54%), and αα//^-20.5 (16.37%), while the predominant alleles were - α³·⁷ (n = 76) and -20.5 (n = 72). In β-thalassemia, the leading alleles were c.25_26delAA (codon 8 - AA; 19.74%), c.315 + 1G > A (IVS-II-1; 8.91%), and c.93-21G > A (IVS-I-110; 5.58%), which together accounted for ∼35% of mutant alleles. The large deletional variants, including Sicilian and Turkish (δβ)⁰ deletion, and Hb-Lepore, were also identified, highlighting the importance of deletion-focused assays. Notably, a <i>novel HBA2</i> start-codon variant (c.3G > A; p.Met1Ile, Hb Baku) and a previously unreported splice variant in <i>HBB</i> (c.315 + 3_+4insT) expanded the mutational landscape. The broad spectrum of small sequence variants and large genomic alterations, including rare and novel findings, underscores the limitations of targeted assays and supports the integration of comprehensive NGS-based diagnostics into national screening and prevention programs.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"332-342"},"PeriodicalIF":1.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204693","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}