Hemoglobin最新文献

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 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.

In southern China, α-thalassemia is the most prevalent hereditary monogenic disorder, and deletion variants are the predominant form. Conventional thalassemia diagnosis techniques are numerous, however they are all limited in their ability to detect rare deletions. Here, we discuss a family who sought genetic counseling during their fourth pregnancy after experiencing Hb Bart's hydrops fetalis in two of their previous pregnancies. To ascertain the thalassemia genotype, the family members underwent hematological testing, routine genetic analysis and multiplex ligation-dependent probe amplification (MLPA). The precise deletion locations could not be identified, while MLPA detected an unknown copy number variant. Lastly, a rare 11.1 kb deletion located in the HBA gene (Chr16: 170,832-182,004, GRch38/hg38) was directly identified by single-molecule real-time technology (SMRT) sequencing. Furthermore, we confirmed the compound heterozygosity of --^11.1 allele and --^SEA allele, which contributed to the explanation of the Hb Bart's hydrops fetalis syndrome in the fetuses from the second and third pregnancies. We have first verified a compound heterozygosity for --^11.1 allele and --^SEA allele. This study may provide a reference strategy for the discovery of rare and potentially novel thalassemia variants using a comprehensive method combining SMRT sequencing and conventional diagnostic technology, improving the accuracy and efficacy of thalassemia diagnosis.

Hemoglobin disorders are highly prevalent inherited hematological defects in Southern China. The identification of novel variants in globin genes and accurate assessment of hematological parameters play a crucial role in precise genetic counseling and clinical practice. Peripheral blood samples were collected for hematological analysis, including red blood cell and hemoglobin assessment, while serum ferritin levels were measured to detect iron depletion. Thalassemia carrier identification was conducted in four subjects admitted to Jiangxi Maternal and Child Health Hospital using next-generation sequencing and Gap-PCR due to the high prevalence of thalassemia in Jiangxi Province. The identified rare or novel small nucleotide variants were subsequently validated through Sanger sequencing. A total of four novel variants were identified incidentally in four unrelated subjects, including HBA1: c.300G > C (p.Lys100Asn), HBA2: c.212T > A (p.Val71Glu), HBB: c.28T > A (p.Ser10Thr) and c.167T > C (p.Met56Thr). The proband carrying the c.212T > A and c.300G > C variants exhibited normal hematological findings, while capillary electrophoresis revealed the presence of abnormal hemoglobin fractions at 22.4% and 10.9%. The subjects with variant HBB: c.28T > A and c.167T > C all demonstrated normal hematological findings and normal hemoglobin fraction as determined by capillary electrophoresis or ion exchange high-resolution liquid chromatography (HPLC). The two variants exhibiting abnormal fractions of hemoglobin were designated as Hb Jiangxi (HBA2: c.212T > A) and Hb Fulton (HBA1: c.300G > C). Meanwhile, HBB: c.28T > A and HBB: c.167T > C were referred to as Hb Yichun and Hb Jinxian, respectively. We here reported four novel variants in globin genes and their hematological findings in for unrelated Chinese individuals in Southern China. Our research has expanded the existing genetic spectrum of globin genes and enhanced our understanding of the hematological profiles associated with variant hemoglobin.

This study aimed to analyze the clinical phenotype of the HBA2: c.95G>A mutation in the Chinese population and to provide guidance for clinical diagnosis and genetic counseling. Peripheral blood samples were collected from 16 patients, including 6 newborns, 2 children, and 8 adults. Hematological parameters and hemoglobin electrophoresis were analyzed, and genotypes were identified using methods such as PCR combined with reverse dot blot (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), and DNA sequencing. The results showed that 10 patients had mild anemia, 2 had moderate anemia, and 12 exhibited microcytic hypochromic features with MCV values ranging from 53 to 74.7 fl and MCH values from 16.2 to 25.4 pg. Additionally, 3 cases displayed obvious HbH + HbBarts bands (>15%). Among the 16 cases, various combinations of the HBA2: c.95G>A mutation were observed: one case had -α^3.7 combined with HBA2: c.95G>A, another had -α^4.2 combined with HBA2: c.95G>A, and five had -^SEA combined with HBA2: c.95G>A, while the remaining cases were HBA2: c.95G>A heterozygotes. The study concludes that the HBA2: c.95G>A mutation in the α2 globin gene causes α+ thalassemia. When this mutation is combined with the Southeast Asian deletion (-^SEA), it results in HbH disease, characterized by moderate microcytic hypochromic anemia and the presence of HbH + HbBarts bands.

Patients suffering from thalassemia are recipients of routine transfusions leading to hemosiderosis. Taking iron chelating agents is mandatory. Several studies have shown different results regarding the occurrence of kidney complications in thalassemia patients who received iron-chelating agents. In this study, we were looking for kidney complications by examining human NAG urine/serum and NGAL urine/serum in thalassemia community in East Java community. The study was conducted cross-sectionally in the thalassemia community in East Java with a total sample of 91 patients aged 13-48 years. All thalassemia patients filled in demographic data, transfusion routines, duration of taking iron chelating agents, and length of time diagnosed with thalassemia. Laboratory tests included routine blood tests for ferritin, ureum, serum creatinine, human NAG urine or serum, and human NGAL urine or serum. Comparison tests (t-test, Mann-Whitney, and ANOVA, Kruskal-Wallis) were conducted to see if there were significant differences in the levels of human NAG urine and human NGAL urine serum based on age, sex, blood group, duration of transfusion, routine of transfusion, duration of taking iron chelating agents, and types of iron chelating drugs. Multivariate analysis was conducted to see whether some of these categories were related to abnormalities in human NAG urine or serum and human NGAL urine or serum. All 91 patients had normal creatinine values, yet some had abnormal serum NAG. There is a significant difference in urine human NAG and urine human NGAL levels at ages over 23 years (p = 0.05 and p = 0.01). Significant differences in human NGAL serum were also found in working and student patients (p = 0.028). Serum NGAL also differed in those taking deferasirox (p = 0.030) and significantly different human NGAL urine was also found in iron overload status (Ferritin ≥ 1000 ng.ml) (p = 0.006). There is no difference between human NAG urine/serum and human NGAL urine/serum based on sex, body mass index, blood type, hemoglobin less than 10 g/dl, routine transfusion once a month, duration of using iron chelation for more than 10 years, or splenomegaly status (splenomegaly, splenectomy, or no splenomegaly). The multivariate logistic regression results showed that age above 23 was a factor associated with abnormal urine human NAG levels (aOR = 3.79, 95% CI = 1.08-13.28). Students (aOR = 4.89, 95% CI = 1.48-16.16) with ages above 23 years (aOR = 3.69, 95% CI = 1.09-12.43) showed higher risk for an abnormal serum human NGAL levels. Patients with beta-thalassemia major exhibit noticeable tubular damage. Further research is encouraged to determine other factors behind tubular damage in the thalassemia community, particularly in Indonesia.

Hereditary hemoglobinopathies, particularly β-thalassemia, are highly prevalent in Azerbaijan, posing a significant public health challenge. In response, the Azerbaijani government implemented a national prevention program that includes mandatory premarital screening and prenatal diagnosis for at-risk couples, aiming to mitigate the impact of these diseases. This report covers the first five years of the program, beginning in 2015. Among 287 identified at-risk couples, 271 fetal samples were analyzed, revealing that 148 were carriers, 63 were affected, and 60 were unaffected. In nearly all cases, affected pregnancies were terminated. The most common mutations detected were Codon 8 [-AA], IVS-II-1 [G > A], and IVS-I-110 [G > A] in the HBB gene. Since the program's inception, the birth rate of affected children has significantly decreased, making this established approach a valuable model for other regions facing similar challenges with autosomal recessive disorders.

In a previously reported equilibrium study of the reaction of 5,5'-dithiobis(2-nitrobenzoate), DTNB, with various carbonmonoxyhemoglobins over the pH range 5.6 to 9, we obtained contradictory results on the influence of the allosteric effector inositol hexakisphosphate (inositol-P₆) on the DTNB reaction. For this reason, we replaced the carbonmonoxyhemoglobins with oxyhemoglobins and investigated the effect of inositol-P₆ on the equilibrium and kinetics of their reactions with DTNB over the same pH range. We found that there are two sets of oxyhemoglobins: (i) In guinea fowl (major) and in dog oxyhemoglobin, inositol-P₆ decreases both the DTNB affinity and the apparent second-order rate constant of the DTNB reaction; and (ii) in the major and minor goat oxyhemoglobins, inositol-P₆ increases each of these two parameters. The x-ray structure of guinea pig methemoglobin shows that it has the R2 quaternary structure. Inositol-P₆ decreased the DTNB affinity of guinea pig oxyhemoglobin throughout our experimental pH range. On the basis of the guinea pig result, we associate the oxyhemoglobins in set (i) with the R2 quaternary structure and those in set (ii) with the R quaternary structure. We conclude that oxyhemoglobins that do not belong to either of these two sets - those of guinea fowl (minor), horse (major), donkey and human - contain equilibrium mixtures of the R and R2 quaternary structures.

Beta-thalassemia is an inherited disorder prevalent in Thailand and Southeast Asia. Several molecular techniques for identifying β-thalassemia mutations have been reported. Next-generation sequencing (NGS) is a type of effective molecular testing with high throughput and accuracy. Hence, this study aims to evaluate a novel barcode-tagged NGS approach based on a short-read assay. A total of 258 samples with 54 different β-thalassemia genotypes related to 32 mutations were gathered and evaluated. A library was constructed with the BTSeq^TM kit and sequencing was performed on the Illumina NGS machine. The validation results showed 98.45% concordance with conventional genotypes. Less discordant results (1.55%) were limited to insertional mutations and included one case of each of the following: HBB:c.27dupG, HBB:c.85dupC, HBB:c.216dupT, and HBB:c.440_441dupAC. Five single-nucleotide polymorphisms that derived from the NGS results were also analyzed in terms of allele frequency and revealed significant differences between the wild types and other β-genotypes. Furthermore, this paper is the first to describe rare single-nucleotide polymorphisms including IVS II-109 (C/T), IVS II-258 (G/A), IVS II-613 (T-C), and IVS II-806 (G/C). Interestingly, the C allele of IVS II-806 was found to have 100% linkage with two cases of Hb Tak. The haplotype and phylogenetic analysis was also constructed based on variants and revealed three clusters in the Hb variants, which represented their evolution and genetic background. Finally, NGS with the barcode-tagged method has a high throughput, which is suitable for large population screening. Its cost effectiveness and less complicated process promote its application in further works.