Hemoglobin最新文献

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 (HBA2: 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.

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 (P = 0.027, P = 0.0007, and P = 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 (P = 0.006 and P < 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.

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.

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 SUPT5H 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 SUPT5H 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 in silico 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 SUPT5H 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.

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.

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, XmnI-^Gγ rs7482144, BCL11A 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 (p < 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 XmnI-^Gγ rs7482144 and BCL11A 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 XmnI-^Gγ rs7482144 and BCL11A rs766432 polymorphisms.

The knowledge of the prevalence and molecular basis of β-hemoglobinopathies constitutes an important prerequisite for an effective prevention program. To address this issue in Iraq's capital, Baghdad, a total of 12526 individuals (6263 couples) attending three main Premarital Screening centers were enrolled. Individuals were labeled as β-hemoglobin disorders based on full blood counts and high-performance liquid chromatography. For those identified as β-thalassemia trait, molecular characterization was achieved by multiplex PCR and reverse hybridization, followed by next-generation sequencing where appropriate. The prevalence of β-thalassemia and δβ-thalassemia traits were 3.5% and 0.01% respectively. For structural variants: sickle cell, hemoglobin D, C, and E traits were documented in 0.37%, 0.07%, 0.05%, and 0.04% respectively. Twenty-two couples were identified as couples at risk of having affected babies with hemoglobinopathies (3.5/1000). A total of 23 different β-thalassemia mutations were identified in studied samples, the eight most frequent of which were IVS-II-I (G > A), IVS-I-110 (G > A), IVS-I-6 (T > C), Codon 44 (-C), IVS-I-5 (G > C), IVS-I-1 (G > A), IVS-I-130 (G > C), and IVS-II-745 (C > G), accounting for 74.7% of the total mutations. In conclusion, the study illustrates the heterogeneity of β-thalassemia mutations in Iraq's capital, and identified several service indicators for prevention. Accordingly, it constitutes an important step in the setup for an effective prevention program of hemoglobinopathies.

In 296 patients with homozygous sickle cell disease (HbSS) detected during the screening of 100,000 deliveries between 1973-1981, chronic hypersplenism defined as a spleen measuring ≥4 cm below the costal margin with evidence of prolonged red cell sequestration occurred in 30 (10.1%) subjects, 23 resolved by splenectomy and 7 resolved spontaneously. Median age at splenectomy was 4.8 years and following splenectomy, median values for hemoglobin increased by 2.3 g/dL, reticulocytes fell by 8.3%, total nucleated cells fell by 2.2%, and platelets increased by 29,813 × 10⁹/dL. Mean splenic weight at splenectomy was 340 g representing 0.5%-4.9% of post-splenectomy body weight. Following splenectomy, height increased at a greater rate than in a matching period for controls (95% CI 0.11-4.06. p = 0.04). Risk factors for hypersplenism, did not differ among commonly used determinants of sickling, fetal hemoglobin (HbF), α globin gene number, or β globin haplotype. A history of acute splenic sequestration preceded hypersplenism more commonly among splenectomized cases (20/23 compared with 0 of 7 resolving spontaneously (Fishers exact test p < 0.001). Factors causing hypersplenism remain largely unknown but splenectomy after a period of monitoring for spontaneous regression, improves hematology and growth.

Microcytosis of red cells and mild anemia are common in thalassemia carriers but those phenotypes are not specific. It is really a challenge for clinical interpretation of those variants. Co-segregation with disease in affected family members or specific phenotypes such as the abnormal Hb H are very helpful to assess the pathogenicity of rare variants. HBA2 c.244delT was only reported in a 19-year-old woman with mild microcytosis and hypochromia. There was no other information about this variant reported before. We first described the case of this variant compounded with SEA deletion who presented with moderate anemia. Co-segregation analysis was confirmed by Sanger sequencing. Our study gave evidence for predicting the pathogenicity of this rare missense variant.