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Clinical and Applied... 2022About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing... (Review)
Review
About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing methods would cause missed diagnosis of partial static thalassemia. Here, we reviewed and summarized a set of simple and clinically feasible thalassemia detection protocols adopted by the Prenatal Diagnosis and Reproductive Center of our hospital. From January 1, 2015, to December 31, 2020, 31 512 peripheral blood samples and 3828 prenatal samples were collected in our study. All the peripheral blood samples were performed through thalassemia screening by routine blood tests and hemoglobin electrophoresis and gene detection. The prenatal diagnosis would be implemented for the fetus if the parents were carriers of the same type of thalassemia. A total of 6137 (19.48%) cases were diagnosed as thalassemia, in which 4749 (15.07%) were α-thalassemia, 1196 (3.80%) were β-thalassemia and 192 (0.61%) were co-inheritance of α- and β-thalassemia. For prenatal samples, 3160 (82.55%) cases were diagnosed as thalassemia, in which 2021 (52.80%) were α-thalassemia, 997 (26.05%) were β-thalassemia and 142 (3.71%) were co-inheritance of α- and β-thalassemia. In addition, we also found five novel mutations, including NC_000016.9:g.223681-227492del3812; HBA1: c.301-31_301-24delCTCGGCCCinsG; HBA2: c.95+7C>T for α-thalassemia and HBB: c.263_276delCACTGAGTGAGCTG; HBB: c.315+143G>A for β-thalassemia. The present study updates the epidemiological characteristics and mutation spectrum of thalassemia in Southern China and demonstrated five novel mutations. Our research provides a reference for clinical diagnosis and treatment, prenatal diagnosis, or reproductive genetic counseling for patients with thalassemia in Guangdong.
Topics: China; Female; Genotype; Humans; Molecular Epidemiology; Mutation; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia; beta-Thalassemia
PubMed: 35979587
DOI: 10.1177/10760296221119807 -
Genetics and Molecular Research : GMR Oct 2008Hemoglobin and globin genes are important models for studying protein and gene structure, function and regulation. We reviewed the main aspects of regulation of human... (Review)
Review
Hemoglobin and globin genes are important models for studying protein and gene structure, function and regulation. We reviewed the main aspects of regulation of human alpha-globin synthesis, encoded by two adjacent genes (alpha(2) and alpha(1)) clustered on chromosome 16. Their expression is controlled mainly by a regulatory element located 40 kb upstream on the same chromosome, the alpha-major regulatory element, whose activity is restricted to a core fragment of 350 bp, within which several regulatory protein binding sites have been found. Natural deletions involving alpha-major regulatory element constitute a particular category of alpha-thalassemia determinants in which the alpha-globin genes are physically intact but functionally inactive.
Topics: Gene Expression Regulation; Humans; Regulatory Sequences, Nucleic Acid; alpha-Globins; alpha-Thalassemia
PubMed: 19048483
DOI: 10.4238/vol7-4gmr472 -
Archives of Razi Institute Jun 2022The prevalence of alpha-thalassemia as a major health problem in the south of Iraq has highlighted the necessity of investigations and screening of patients with...
The prevalence of alpha-thalassemia as a major health problem in the south of Iraq has highlighted the necessity of investigations and screening of patients with thalassemia. The present study aimed to characterize the spectrum of alpha-globin gene mutations in patients who were followed up in a genetic diseases center in Thi-Qar province. A total of 30 subjects were collected from thalassemia patients and 15 cases as the control group. Polymerase chain reaction (PCR) and direct sequencing were performed for functionally regions of the gene (exon 1 and exon 2). The fragment size amplified was 442 bp in the Exon 1 region and 324 bp in the Exon 2 region of α-globin. The molecular analysis of the sequence of PCR products revealed that 13 point mutation within the α-thalassemia gene included deletion and substitution mutation, while the rest of the mutations were in the intron site of the gene. These results indicated that mutations may constitute a risk of developing hemophilia B disease. Molecular mechanisms in the expression of globin genes are used to help manage patients with thalassemia.
Topics: alpha-Globins; alpha-Thalassemia; Iraq; Mutation; Point Mutation; Humans
PubMed: 36618297
DOI: 10.22092/ARI.2022.357209.1997 -
International Journal of Environmental... Oct 2020Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's... (Meta-Analysis)
Meta-Analysis
Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger's tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, -value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.
Topics: Asia, Southeastern; Humans; Prevalence; alpha-Thalassemia
PubMed: 33050119
DOI: 10.3390/ijerph17207354 -
Genetics in Medicine : Official Journal... Feb 2011
Review
Topics: Drug Substitution; Female; Gene Deletion; Genetic Association Studies; Genetic Counseling; Genetic Testing; Hemoglobins, Abnormal; Heterozygote; Humans; Male; alpha-Globins; alpha-Thalassemia
PubMed: 21381239
DOI: 10.1097/GIM.0b013e3181fcb468 -
Medicine Mar 2022There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α-... (Observational Study)
Observational Study
There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α- and β-thalassemia genotypes among pregnant women in Hubei Province, and to explore the clinically applicable screening approach, as well as to investigate the pregnancy outcomes of α- and β-thalassemia carriers.Pregnant participants were recruited from 4 hospitals for the screening of α- and β-thalassemia mutations in Hubei Province. Polymerase Chain Reaction and flow cytometry methods were used to examine α- and β-thalassemia mutations. The hematological parameters and pregnancy outcomes of α- and β-thalassemia carriers were obtained from the hospital information system. The chi-square tests were used to evaluate the difference in hematological parameters between pregnant thalassemia carriers and the control group.Among 11,875 participants, 414 (3.49%) were confirmed with α-thalassemia carriers, 228 (1.92%) were confirmed with β-thalassemia carriers, and 3 (0.03%) were confirmed with both α- and β-thalassemia carriers. The frequency of -α3.7 accounted for 2.05% and it was the most frequent genotype of α-thalassemia; the proportion of IVS-II-654 was 0.85% and it was the most frequent genotype of β-thalassemia in Hubei Province. Furthermore, the proportion of patients with low mean corpuscular volume (MCV) or mean cell hemoglobin (MCH) values was accounted for 36.64% and 93.97% among α-thalassemia and β-thalassemia carriers, respectively. And participants with normal MCV and MCH values were accounted for 95.07% among non-thalassemia participants. High prevalence of pregnancy-induced diabetes (16.97%), preterm birth (9.96%), pregnancy-induced hypertension (8.12%), and low birth weight (5.90%) were observed among pregnant thalassemia carriers.MCV and MCH values were suggested to apply on the preliminary screening of pregnant β-thalassemia; however, it's unpractical on that of α-thalassemia. Furthermore, thalassemia carriers might have a high risk of negative pregnancy outcomes. These findings could be useful for the preliminary screening of thalassemia and perinatal care for the pregnant thalassemia carriers.
Topics: China; Diabetes, Gestational; Female; Genotype; Hemoglobins; Humans; Hypertension, Pregnancy-Induced; Infant, Low Birth Weight; Infant, Newborn; Male; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Hematologic; Pregnant Women; Premature Birth; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 35244037
DOI: 10.1097/MD.0000000000028790 -
Biomedical and Environmental Sciences :... Oct 2021Thalassemia is a group of genetically heterogeneous diseases characterized by hemolytic anemia. To investigate molecular characteristics of α- and β-thalassemia among...
Thalassemia is a group of genetically heterogeneous diseases characterized by hemolytic anemia. To investigate molecular characteristics of α- and β-thalassemia among young individuals of marriageable age in Guangdong Province, 24,788 subjects with suspected thalassemia were genetically tested for α- and β-thalassemia by Gap-PCR and reverse dot blot during 2018-2019. For suspected rare thalassemia cases, DNA sequencing was performed to identify rare and unknown thalassemia gene mutations. A total of 14,346 thalassemia carriers were detected, including 7,556 cases of α-thalassemia with 25 genotypes and 8 α-gene mutations identified, 5,860 cases of β-thalassemia with 18 genotypes and 18 β-gene mutations identified, and 930 cases of compound α/β-thalassemia. Among them, the frequency of -- deletion was the highest in α-thalassemia (66.01%), followed by -α (17.98%) and -α (8.22%), and the frequency of CD41-42 (-TCTT) mutation was the highest in β-thalassemia (38.38%), followed by IVS-II-654 (C > T) (25.67%), -28 (A > G) (15.76%), and CD17 (10.01%). In addition, 5 rare mutations (--THAI and HKαα, CD113, -90, and CD56) were found in the study population. Our results revealed molecular epidemiological background of α- and β-thalassemia in Guangdong Province, which can support optimization of thalassemia prevention and control strategies. We demonstrated that thalassemia is heterogeneous with significant geographical differences and population specificity.
Topics: Adult; China; Female; Genotype; Humans; Male; Middle Aged; Mutation; Sequence Analysis, DNA; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 34782049
DOI: 10.3967/bes2021.112 -
Saudi Medical Journal Nov 2015Alpha-thalassemia (α-thal) is a disorder caused by the deletion of single or double α-globin genes, and/or point mutations in the α-globin genes. There are 2 common... (Review)
Review
Alpha-thalassemia (α-thal) is a disorder caused by the deletion of single or double α-globin genes, and/or point mutations in the α-globin genes. There are 2 common types of α-globin genes; HBA2 and HBA1. Recently, it has been discovered that the HBA2 gene is replaced by a unique HBA12 gene convert in 5.7% of the Saudi population. The α-globin genes have been emerging as a molecular target for the treatment of β-thalassemia (β-thal). Hence, it is essential to understand the molecular nature of α-globin genes to treat the most prevalent hemoglobin disorders, such as sickle cell disease, α-thal, and β-thal prevalent in the Kingdom of Saudi Arabia. Thirty-two different α-globin genotypes have been observed in the Saudi population. This review outlines the classification of the α-globin genes on the basis of their molecular nature and complex combinations of α-globin genes, and their variants predominant in Saudis.
Topics: Chromosome Mapping; Humans; Saudi Arabia; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 26593158
DOI: 10.15537/smj.2015.11.12704 -
Blood Jan 2005Abnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia.... (Review)
Review
Abnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired alpha-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired alpha-thalassemia are now recognized: acquired deletion of the alpha-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic down-regulation of alpha-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of alpha-thalassemia arising in a clonal myeloid disorder, and we discuss howATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms.
Topics: Hematologic Neoplasms; Humans; Myelodysplastic Syndromes; alpha-Thalassemia
PubMed: 15358626
DOI: 10.1182/blood-2004-07-2792 -
Journal of Clinical Laboratory Analysis Jun 2021Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler...
BACKGROUND
Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha-thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha-thalassemia and G6PD(A ) variant with abnormal TCD velocities among Nigerian children with SCA.
METHODS
One hundred and forty-one children with SCA were recruited: 72 children presented with normal TCD (defined as the time-averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha-thalassemia (the α-3.7 globin gene deletion) was determined by multiplex gap-PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism-polymerase chain reaction.
RESULTS
The frequency of α-thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α-/ α α: 41.7%, α -/ α -: 11.1%] versus 21/69 (30.4%) [α-/ α α: 27.5%, α -/ α -: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α-thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20-0.78, p = 0.007]. However, the frequencies of G6PDA variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).
CONCLUSION
Our study reveals the protective role of α-thalassemia against the risk of abnormal TCD in Nigerian children with SCA.
Topics: Adolescent; Anemia, Sickle Cell; Blood Flow Velocity; Case-Control Studies; Cerebrovascular Circulation; Child; Child, Preschool; Female; Follow-Up Studies; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Nigeria; Prognosis; Stroke; Ultrasonography, Doppler, Transcranial; alpha-Thalassemia
PubMed: 33938598
DOI: 10.1002/jcla.23802