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Gene Jul 2017Thalassemia is one of the most common hereditary blood disorders. Epidemiological data regarding the occurrence and distribution of thalassemia is important for...
Thalassemia is one of the most common hereditary blood disorders. Epidemiological data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies. The objective of this study was to update and reveal the prevalence of thalassemia and mutation spectrum in the Baise region of southern China. We screened 47,500 individuals from Baise region by hematological and genetic analysis. Totally, 11,432 (24.07%) subjects were diagnosed as being carriers and patients of thalassemia, including 7290 (15.35%) subjects with α-thalassemia, 3152 (6.64%) subjects with β-thalassemia and 990 (2.08%) subjects with both α-thalassemia and β-thalassemia. Ten α-thalassemia mutations and 31 genotypes were identified in the α-thalassemia carriers and patients. Meanwhile, 13 β-thalassemia mutations and 26 genotypes were characterized in the β-thalassemia carriers and patients. Furthermore, the true prevalence of nondeletional mutations and Thailand type (-THAI) deletion mutation were first reported in this study. In addition, three cases of αα/ααα3.7, five cases of HKαα/αα and two rare β-globin mutations, -86 (G>C) and CD 121 (G>T) were first identified in the Chinese Zhuang ethnic populations. Our data indicated that there was great heterogeneity and extensive spectrum of thalassemias in the Baise populations. The findings will be useful for genetic counseling and prevention of severe thalassemia in this region.
Topics: China; Gene Frequency; Hemoglobins, Abnormal; Humans; Mutation; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 26877226
DOI: 10.1016/j.gene.2016.02.014 -
Journal of Clinical Laboratory Analysis Mar 2018To date, there has been no systematic study of DNA-based prenatal diagnosis of thalassemia in pregnant Hakka women in southern China.
BACKGROUND
To date, there has been no systematic study of DNA-based prenatal diagnosis of thalassemia in pregnant Hakka women in southern China.
METHODS
A total of 279 pregnant Hakka women with confirmed cases of thalassemia who had been treated at the Meizhou People's Hospital in China's Guangdong Province from January 2014 to December 2016 were here enrolled. Genomic DNA was extracted from peripheral blood of couples and villus, amniotic fluid, or fetal cord blood. DNA-based diagnosis was performed on the tissues of fetuses whose parents had tested positive for α- and β-globin gene mutations were found using polymerase chain reaction (PCR) and flow-through hybridization technique. Follow-up visits were performed 6 months after the fetuses were born. Prenatal diagnosis was performed on 279 fetuses in at-risk pregnancies.
RESULTS
Here, 211 α-thalassemia fetuses were confirmed, including 41 (19.43%) that tested positive for Bart's hydrops syndrome and 15 (7.11%) for Hb H disease. There were 103 (48.81%) heterozygotes. β-thalassemia was confirmed in 68 fetuses, including 23 (33.82%) with severe thalassemia and 27 (39.71%) heterozygotes. Another 12 cases were confirmed with α+β-thalassemia, including three cases of severe β-thalassemia. DNA-based testing prenatal diagnosis of thalassemia was found to be highly reliable.
CONCLUSIONS
Our findings provide key information for clinical genetic counseling of prenatal diagnosis for major thalassemia in pregnant Hakka women in southern China.
Topics: China; DNA Mutational Analysis; Female; Fetus; Humans; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Diagnosis; Retrospective Studies; alpha-Thalassemia; beta-Thalassemia
PubMed: 28771834
DOI: 10.1002/jcla.22306 -
Gene May 2022Gap- polymerase chain reaction (PCR), reverse dot-blot assay (RDB), real-time PCR based multicolor melting curve analysis (MMCA assay), multiplex ligation-dependent...
Gap- polymerase chain reaction (PCR), reverse dot-blot assay (RDB), real-time PCR based multicolor melting curve analysis (MMCA assay), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing are conventional methods to diagnose thalassemia but all of them have limitations. In this study, we applied single-molecule real-time (SMRT) sequencing following multiplex long-range PCR to uncover rare mutations in nine patients and their family members. The patients with different results between Gap-PCR and MMCA assay or with phenotype not matching genotype were included. Using SMRT sequencing, we first identified the carriers with ααα/HKαα, -αα/αα (chr16:172,648-173,409), αα/αα (in a trans configuration), two cases with novel gene rearrangements and another case with a novel 341 bp insertion in α-globin gene cluster, respectively. One carrier with --/ααα, and two carriers with the coexistence of globin variant and an α-globin gene duplication were also found. Most importantly, we could determine two defects in α-globin gene cluster being a cis or trans configuration in a single test. Our results showed that SMRT has great advantages in detection of α-globin gene triplications, rare deletions and determination of a cis or trans configuration. SMRT is a comprehensive and one-step method for thalassemia screening and diagnosis, especially for detection of rare thalassemia mutations.
Topics: Genotype; Humans; Multiplex Polymerase Chain Reaction; Mutation; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 35306112
DOI: 10.1016/j.gene.2022.146438 -
Hematology (Amsterdam, Netherlands) Dec 2021Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is...
INTRODUCTION
Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited.
METHODS
This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations.
RESULTS
One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia
CONCLUSIONS
The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.
Topics: Adolescent; Adult; Female; Ferritins; Humans; Iron; Liver; Male; Middle Aged; Thailand; Young Adult; alpha-Thalassemia
PubMed: 34238133
DOI: 10.1080/16078454.2021.1943829 -
American Journal of Hematology Oct 2022α-Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We...
The pleiotropic effects of α-thalassemia on HbSS and HbSC sickle cell disease: Reduced erythrocyte cation co-transport activity, serum erythropoietin, and transfusion burden, do not translate into increased survival.
α-Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12-year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α-thalassemia strongly reduces erythrocyte potassium chloride co-transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α-thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α-thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno-protective effect of α-thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10 ). We found patients with α-thalassemia had a reduced annualized transfusion burden in both HbSS and HbSC, but α-thalassemia had no impact on annualized admission rates in either group. Finally, in a larger cohort, we report a median survival of 62 years in patients with HbSS (n = 899) and 80 years in those with HbSC (n = 240). α-thalassemia did not influence survival in HbSS, but a nonsignificant trend was seen in those with HbSC.
Topics: Anemia, Sickle Cell; Cations; Erythrocytes; Erythropoietin; Hemoglobin SC Disease; Hemoglobin, Sickle; Humans; alpha-Thalassemia
PubMed: 35802781
DOI: 10.1002/ajh.26652 -
International Journal of Laboratory... Feb 2017Bahrain has high prevalence rates of sickle cell and thalassemia in the population. This study reports the frequencies and phenotypic characteristics of α- and/or... (Clinical Trial)
Clinical Trial
INTRODUCTION
Bahrain has high prevalence rates of sickle cell and thalassemia in the population. This study reports the frequencies and phenotypic characteristics of α- and/or β-thalassemia associated with sickle-cell disease (SCD) in a tertiary care hospital.
METHODS
Adult SCD patients (n = 200) were screened for the common α- and β-thalassemia alleles prevalent in the region using molecular techniques. Results of CBC, hemoglobin analysis, and average annual frequencies of severe pain episodes and numbers of transfused red cell units were documented.
RESULTS
Patients were grouped on the basis of molecular studies as sickle-cell anemia (SS, n = 131), SS/α-thalassemia with three normal genes (n = 27), SS/α-thalassemia with two normal genes (n = 11), sickle-β-thalassemia (Sβ, n = 23), and Sβ with co-inherited α-thalassemia (n = 8). Identified α-thalassemia determinants were -α (n = 52), -α (n = 4), α α (n = 1), and α α (n = 1). All β-thalassemia alleles were β defects. Sickle-thalassemia association resulted in higher hemoglobin, hematocrit, and erythrocyte counts with reduced MCV and reticulocytes. Significant clinical associations were as follows: increased severe pain frequency with α-thalassemia (three-gene group); red cell transfusion with β-thalassemia alleles and female gender.
CONCLUSION
One-third of patients with SCD co-inherited α- and/or β-thalassemia alleles and these associations explained some of the observed phenotypic variability. A low prevalence of nondeletion α-thalassemia alleles was observed in these patients. The most significant disease amelioration occurred in SCD associated with two α-thalassemia alleles.
Topics: Adult; Alleles; Anemia, Sickle Cell; Bahrain; Female; Gene Frequency; Humans; Male; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 27981798
DOI: 10.1111/ijlh.12577 -
Thrombosis Research Oct 2016Thalassemia intermedia (TI), a non-transfusion dependent thalassemia, is divided into α-thalassemia, such as HbH disease, and β-thalassemia diseases, such as HbE/β...
Thalassemia intermedia (TI), a non-transfusion dependent thalassemia, is divided into α-thalassemia, such as HbH disease, and β-thalassemia diseases, such as HbE/β thromboembolism (TE) in TI has been mostly reported in β-thalassemia diseases with incidence rates of 3.9-29%. The present study enrolled 60 patients with α-thalassemia intermedia. The control groups were thalassemia major (TM) consisting of 17 patients diagnosed with β-thalassemia diseases, 24 patients diagnosed with splenectomized β-thalassemia diseases and 25 normal subjects. The mean±SD ages were 12.9±5.3, 15.0±3.8, 15.7±4.1 and 12.3±2.5years respectively. The coagulation markers in α-thalassemia patients, including D-dimer, thrombin-antithrombin complex (TAT) and prothrombin fragment (F1.2), were not significantly different compared to the levels in normal subjects. Similar results were found for the thromboelastometry, which is a method to assess global hemostasis involving the functions of coagulation and anticoagulation proteins, fibrinolysis and platelets. The hypercoagulability could be demonstrated in TM by high TAT in severe β-thalassemia patients and high TAT and D-dimer, shortened CT and CFT, high alpha angle, A20 and MCF only in the splenectomized β-thalassemia patients.
Topics: Adolescent; Child; Female; Hemostasis; Humans; Male; Thrombelastography; alpha-Thalassemia
PubMed: 27572718
DOI: 10.1016/j.thromres.2016.08.024 -
Journal of Clinical Laboratory Analysis Mar 2024Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have...
BACKGROUND
Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have investigated the molecular characterization of α- and β-thalassemia in children from Guizhou, China.
METHODS
Between January 2019 and December 2022, a total of 3301 children, aged 6 months to 18 years, suspected of having thalassemia underwent molecular analysis.
RESULTS
Out of the total sample, 824 (25%) children were found to carry thalassemia mutations. The carrier rates of α-thalassemia, β-thalassemia, and α + β-thalassemia were determined as 8.1%, 15.6%, and 1.3%, respectively. Approximately 96.5% of the α-thalassemia gene mutations were --SEA (51%), αα (20.9%), -α (19.6%), and -α (5.0%). The most prevalent mutations of β-thalassemia were β (41.5%), β (37.7%), and β (11.3%). Additionally, we identified rare cases, including one case with αα/αα, two cases with triplicated α-thalassemia (one case with ααα/ααα and β/β and the other with ααα/αα and βE /β), and also one case with α α/-α and β/β.
CONCLUSIONS
Our study findings provide important insights into the heterogeneity of thalassemia carrier rates and molecular profiles among children in the Guizhou region. The findings support the development of prevention strategies to reduce the incidence of severe thalassemia in the future.
Topics: Child; Humans; Adolescent; beta-Thalassemia; alpha-Thalassemia; Genotype; China; Mutation
PubMed: 38506255
DOI: 10.1002/jcla.25022 -
European Journal of Medical Genetics 2014We report the general phenotype severity and the hematological presentation in a cohort of 125 sickle cell anemia (SCA) patients with identical homozygous HbS/S genotype...
We report the general phenotype severity and the hematological presentation in a cohort of 125 sickle cell anemia (SCA) patients with identical homozygous HbS/S genotype and categorized by identical β(S) haplotype, both with and without alpha thalassemia. No clear general phenotype correlation was found when patients were compared regardless of the haplotype but overall, patients with homozygous alpha thalassemia (α-/α-) had the highest Hb, HCT, RBC and the lowest MCV, MCH and MCHC levels. When patients with identical haplotype were compared, the mildest hematological and clinical conditions were observed in patients of the Asian/Asian haplotype, also known as Arab-Indian haplotype, and carriers of α-thalassemia, suggesting an additional ameliorating effect of alpha thalassemia. In conclusion, our results show that alpha thalassemia improves the hematological conditions but amelioration of the general disease severity is only noticed when compared in cohorts of the same haplotype.
Topics: Anemia, Sickle Cell; Haplotypes; Hemoglobin, Sickle; Homozygote; Humans; Oman; Severity of Illness Index; alpha-Thalassemia
PubMed: 25266642
DOI: 10.1016/j.ejmg.2014.09.005 -
Nigerian Journal of Clinical Practice Jun 2021Sickle cell disease (SCD) is a monogenic, phenotypically highly variable disease with multisystem pathology. The phenotypic heterogeneity of SCD is attributed to...
BACKGROUND
Sickle cell disease (SCD) is a monogenic, phenotypically highly variable disease with multisystem pathology. The phenotypic heterogeneity of SCD is attributed to environmental and genetic factors such as fetal hemoglobin and co-inheritance of α-thalassemia.
OBJECTIVES
To look for different types of α-thalassemia gene mutations among SCD patients and evaluate the influence of the co-inheritance of α-thalassemia on clinical and hematological variables.
METHODS
This cross-sectional analytical study included 765 SCD patients, and 150 patients (with low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH) and normal serum ferritin levels) were tested for α-thalassemia gene mutations. Multiplex PCR and reverse hybridization and sequencing for both α genes using the Vienna Lab Strip Assay PCR study were performed using conventional PCR technology.
RESULTS
Out of 150 patients tested for α-thalassemia gene mutations, 141 patients were found to have one or more of the mutational types, representing 18.4% of all studied SCD patients. The most common mutations found were the - deletion (76.6%), followed by the - deletion (12.1%), mutant α2 (Saudi type) (9.2%), and -- double gene deletion (7.8%). Acute painful episodes did not differ significantly in sickle cell anemia (SCA) patients with or without α-thalassemia, although the co-inheritance of α-thalassemia has a protective role against many disease-related complications. However, this role was not observed with other types of SCD. The means of red blood cell count, hemoglobin, and hematocrit were significantly higher, while the MCV, MCH, reticulocyte count, and hemoglobin A2 percentage were significantly lower in patients with α-thalassemia gene mutations than in those without α-thalassemia gene mutations (P < 0.05).
CONCLUSIONS
The co-inheritance of α-thalassemia and SCA confers protection against many disease-related complications and is associated with improved hematological indices. However, this protection was not noticed in patients with other types of SCD.
Topics: Anemia, Sickle Cell; Cross-Sectional Studies; Erythrocyte Indices; Humans; Mutation; alpha-Thalassemia
PubMed: 34121736
DOI: 10.4103/njcp.njcp_11_20