Hemoglobin最新文献

Background: Sickle cell disease (SCD) is prevalent in Saudi Arabia. This study evaluates the long-term survival rates of a cohort of SCD patients.

Methods: This observational cohort study was conducted at King Saud University Medical City from January 2009 to September 2023. We enrolled 223 SCD patients between 2009 and 2014, collecting comprehensive data at baseline and during follow-up. The primary endpoint was overall survival.

Results: The cohort had a median follow-up of 11.5 years, totaling 2,118 patient-years. The recent median age was 28.9 years (12.2-63.8). The survival rates at ages 20, 30, 40, and 50 years were 100%, 98.4%, 95.1%, and 89.0%, respectively, with no mortality observed before the age of 20 years. The incidence of mortality was 0.28 deaths per 100 patient-years. Among the six deaths (2.7%), causes included non-Hodgkin lymphoma, acute chest syndrome, and a sepsis-like condition, with three unknown causes. The median age of death was 36.3 years. The increased use of hydroxyurea, from 47% to 80%, was associated with reduced pain crises and acute chest syndrome, and improved hemoglobin and HbF levels. Of the patients, 43 (19.2%) were lost to follow-up, 16 (7.2%) were referred for stem cell transplant, and 16 (7.2%) were followed at other institutions.

Conclusions: This study highlights excellent survival rates for SCD patients in our cohort. Nonetheless, the considerable loss to follow-up highlights the need for strategies to address this issue and larger multicenter studies to confirm our results.

β-thalassemia (thal), hemoglobin (Hb) E, and high Hb F determinants, which are caused by mutations in the β-globin gene cluster, are common genetic disorders in Thailand and Southeast Asia. Prenatal diagnosis is essential for couples at risk to identify severe forms, including homozygous β-thal and Hb E/β-thal. Conventional methods, including reverse dot-blot hybridization and gap-polymerase chain reaction (PCR) for genotyping of point and large deletion mutations, require post-PCR steps, which are time-consuming and costly. This study aimed to develop a rapid and efficient method using monoplex high-resolution melting (HRM) analysis for genotyping of Hb E and 11 β-thal mutations; multiplex HRM analysis for identifying six deletional mutations, including two β⁰-thal mutations (3.5 and 45 kb deletion); and a novel method for detecting four high Hb F determinants, namely, δβ⁰-thal (12.5 kb deletion), HPFH6, Indian inv-del (^Aγδβ)⁰-thal, and Thai del-inv-ins (^Aγδβ)⁰-thal. The developed assays were validated using 182 blinded fetal DNA samples with 41 β-thal genotypes. Different HRM patterns were observed among wild-type, heterozygote, homozygote, and compound heterozygote genotypes. Six deletional mutations showed specific melt curves. This technique demonstrated 100% concordance with conventional methods. The assay showed 100% sensitivity, specificity, and positive and negative predictive values within the limit of detection at DNA concentrations of 8.0 ng/reaction. Finally, this developed assay was efficient in identifying both point mutations and large deletion, convenient, rapid, and cost-effective and did not require post-PCR steps. Thus, this technique has potential for application in prenatal diagnosis of thal and can inform prevention and control programs.

Genotype-phenotype correlation and potential genetic risk in the compound heterozygosity for unstable hemoglobins (UHbs) and α⁰-thalassemia were discussed. Capillary electrophoresis and gene sequencing helped to establish the diagnosis. Hematological analysis showed the following findings: MCV 80.6 fL, MCH 27 pg, HGB 133 g/L, RBC 4.93 × 10¹²/L, Hb A: 94%, Hb X: 3.6% (zone 12) and Hb A₂: 2.4%. DNA analysis revealed the patient was a Hb Pontoise carrier (HBA1: c.191C > A). Hb Pontoise resulted from an GCC > GAC substitution at codon 63 of the HBA1 genes, but carriers were usually asymptomatic or with only borderline hematological abnormalities. Due to mild instability of Hb Pontoise, its diagnosis relied on genetic diagnosis. Considering the high frequency of thalassemia in South China, accurate genotyping and appropriate genetic counseling should be performed for unstable hemoglobin carriers.

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.

This study presents the hematological and genetic analysis of a child with severe β-thalassemia harboring triple heterozygous mutations. The child, diagnosed with anemia at the age of 1 year, became transfusion-dependent and maintained a hemoglobin level of 72.00-84.00 g/L following regular blood transfusions. At the age of 9 years, genetic analysis was conducted using PCR-reverse dot blot (PCR-RDB), Sanger sequencing, and third-generation nanopore sequencing. Sanger sequencing identified a triple heterozygous mutation in the β-globin gene: -28(A > G) (HBB:c.-78A > G), IVS-I-5(G > A) (HBB:c0.92 + 5G > A), and CD 71/72(+A) (HBB:c.216_217insA). Nanopore sequencing further confirmed the genotype as β^{-28(A>G), IVS-I-5(G>A)}/β^{CD 71/72(+A)}. The combination of these mutations represents a rare β-thalassemia genotype in China, contributing to the β-globin gene mutation database for the Chinese population. This study highlights the importance of employing family analysis or third-generation sequencing technologies to clarify complex mutation linkages when Sanger sequencing alone cannot determine the relationship between multiple mutations.

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.

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.

The 3.7 kb deletion is the most common known mutation in the α-globin gene cluster worldwide. The aim of this study is to investigate the most common types of 3.7 kb deletions in the Iranian population and, on the other hand, to compare the extent of deletion of the different reported types.

In this study, 50 Iranian α-thalassemia carriers in whom the 3.7 kb deletion had been previously identified by multiplex gap PCR, were further investigated by MLPA. A map of the region where the 3.7 kb deletion occurs was also created and the extents of the reported types were compared.

Approximately 90% of chromosomes with 3.7 kb deletion in this study had MLPA type D and 10% had MLPA type F. This study showed that subtype I of the 3.7 kb deletion reported by Higgs and his coworkers can be classified into at least 5 MLPA types.

The results of this study can be used to complete the information on the distribution of the 3.7 kb deletion subtypes in different populations. Investigation of further populations using higher resolution methods may lead to more information being obtained in this field.

Children with sickle cell anemia (SCA) experience recurrent vaso-occlusive crises and complications, significantly impacting their health-related quality of life (HRQoL). This study determined HRQoL in 130 children aged 5 -15 years with SCA in The Gambia, compared to 130 age- and sex-matched hemoglobin AA (HbAA) children. HRQoL was measured using the Pediatric Quality of Life Inventory (PedsQL), with scores below 69.7 defined as poor HRQoL. Predictors of poor HRQoL were analyzed using binary logistic regression. The mean ages of children with SCA and HbAA were similar (9.83 ± 2.79 years vs. 9.65 ± 2.84 years, p = 0.598), with a male-to-female ratio of 1.1:1. SCA children showed significantly higher rates of underweight (p = 0.019) and stunting (p = 0.045) compared to HbAA children. HRQoL scores were significantly lower in the SCA group across physical, emotional, social, school, and overall domains (p < 0.001). A majority (57.7%) of SCA children had poor HRQoL. Key predictors of poor HRQoL among SCA children included frequent pain episodes (>3 episodes in the past 12 months; odds ratio [OR] = 1.9, p = 0.028), late diagnosis of SCA (OR = 1.8, p = 0.012), and clinical stroke (OR = 69.3, p = 0.037). This study demonstrates that SCA significantly reduces HRQoL in all domains. Early diagnosis, effective pain management, and prevention of complications like stroke are critical to improving outcomes. Tailored interventions are needed to mitigate the physical and psychosocial burdens of SCA among children in The Gambia.