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Orphanet Journal of Rare Diseases Jun 2020Defective synthesis of the α-globin chain due to mutations in the alpha-globin genes and/or its regulatory elements leads to alpha thalassaemia syndrome. Complete... (Review)
Review
BACKGROUND
Defective synthesis of the α-globin chain due to mutations in the alpha-globin genes and/or its regulatory elements leads to alpha thalassaemia syndrome. Complete deletion of the 4 alpha-globin genes results in the most severe phenotype known as haemoglobin Bart's, which leads to intrauterine death. The presence of one functional alpha gene is associated with haemoglobin H disease, characterised by non-transfusion-dependent thalassaemia phenotype, while silent and carrier traits are mostly asymptomatic.
MAIN BODY
Clinical manifestations of non-deletional in alpha thalassaemia are varied and have more severe phenotype compared to deletional forms of alpha thalassaemia. Literature for the molecular mechanisms of common non-deletional alpha thalassaemia including therapeutic measures that are necessarily needed for the understanding of these disorders is still in demand. This manuscript would contribute to the better knowledge of how defective production of the α-globin chains due to mutations on the alpha-globin genes and/or the regulatory elements leads to alpha thalassaemia syndrome.
CONCLUSION
Since many molecular markers are associated with the globin gene expression and switching over during the developmental stages, there is a need for increased awareness, new-born and prenatal screening program, especially for countries with high migration impact, and for improving the monitoring of patients with α-thalassaemia.
Topics: Female; Gene Expression; Humans; Mutation; Phenotype; Pregnancy; alpha-Globins; alpha-Thalassemia
PubMed: 32600445
DOI: 10.1186/s13023-020-01429-1 -
Best Practice & Research. Clinical... Feb 2017
Topics: Bone Marrow Transplantation; Female; Genetic Counseling; Genetic Testing; Humans; Iron Chelating Agents; Pregnancy; Pregnancy Complications, Hematologic; Preimplantation Diagnosis; Prenatal Diagnosis; alpha-Thalassemia; beta-Thalassemia
PubMed: 28027848
DOI: 10.1016/j.bpobgyn.2016.11.001 -
Hematology (Amsterdam, Netherlands) Dec 2022The 3.7 kb deletion (-α) in the α-globin cluster, which characterizes α-thalassemia, has been reported to have a carrier rate of 4.78% in southern China. Three -α...
OBJECTIVE
The 3.7 kb deletion (-α) in the α-globin cluster, which characterizes α-thalassemia, has been reported to have a carrier rate of 4.78% in southern China. Three -α subtypes have been identified worldwide. However, the -α subtype has not previously been identified in China. Herein, we reported identification of the -α subtype in a Chinese patient.
METHODS
We used gap-PCR and a liquid chip system to detect α-thalassemia mutations. Multiple ligation-dependent probe amplification was performed to detect the large deletion. We finally used Sanger sequencing and single molecule real-time sequencing to characterize and confirm the genotype.
RESULTS
The proband, characterized as -α heterozygous, showed microcytosis and hypochromic red cells, with a mean corpuscular volume of 78 fL and mean corpuscular hemoglobin of 25.4 pg. The proband's mutation was inherited from her father, who had normal blood parameters.
CONCLUSION
We first identified the -α subtype in China. Consequently, all -α subtypes have now been identified in the Chinese population. Therefore, attention should be paid to -α in clinical prenatal diagnosis, given that commonly used methods such as gap-PCR may lead to misdiagnosis or missed diagnosis.
Topics: China; Female; Genotype; Heterozygote; Humans; Pregnancy; alpha-Globins; alpha-Thalassemia
PubMed: 35916627
DOI: 10.1080/16078454.2022.2101913 -
BMC Medical Genetics Aug 2020The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is...
BACKGROUND
The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of patients who were referred for molecular diagnosis over a 20-year period.
METHODS
This is a retrospective study of the α-globin genotypes obtained in the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University from 1994 to 2015. Genotyping was performed by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot blot hybridization (Vienna Lab Strip Assay).
RESULTS
Four hundred samples were characterized and analyzed from individuals aged < 1 month to 80 years, with a median of 6 years from 283 unrelated families. Most (90.8%) were Kuwaiti nationals. The commonest genotype was homozygosity for the polyadenylation-1 mutation (αα/α α) in 33.3% of the samples, followed by heterozygosity (αα/α α) for the same mutation in 32.3%. PA-1 was therefore the most frequent allele (0.59). The frequency of the α (--) allele was 0.017. Rare alleles that were found in very low frequencies included α (--) in a Filipino child, Hb Constant Spring, Hb Adana, and Hb Icaria.
CONCLUSION
There is a wide variety of alpha thalassemia alleles among Kuwaitis, but nondeletional PA-1 is by far the most common cause of the moderate to severe HbH (β4 tetramer) disease phenotype. The α (-) allele is also encountered, which has implications for premarital counseling, especially for the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Child; Child, Preschool; Female; Gene Frequency; Genotype; Humans; Infant; Infant, Newborn; Kuwait; Male; Middle Aged; Retrospective Studies; Young Adult; alpha-Globins; alpha-Thalassemia
PubMed: 32831051
DOI: 10.1186/s12881-020-01105-y -
Hemoglobin May 2022Despite several studies performed in different provinces of Iran to identify the spectrum of α-globin gene mutations, no such study has so far been carried out in Ilam...
Despite several studies performed in different provinces of Iran to identify the spectrum of α-globin gene mutations, no such study has so far been carried out in Ilam Province. A total of 274 individuals, including 201 α-thalassemia (α-thal) carriers and 73 normal subjects, originating from the northern counties of Ilam Province, participated in this study. Analysis of α-globin defects was performed using multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing, which revealed a total of 11 different mutations and 22 different genotypes. The -α (rightward) (NG_000006.1: g.34164_37967del3804), αα (: c.95 + 2_95 + 6delTGAGG), and -α (leftward) deletions were the most prevalent mutations identified in our study, with frequencies of 66.23, 10.09 and 8.33%, respectively. In conclusion, the present study showed that the α-thal mutation spectrum in Ilam Province, at least in the northern part of the province, is different from that in other geographical regions of Iran. These results increase our knowledge about the spectrum and distribution of α-globin gene mutations in Iran.
Topics: Gene Frequency; Genotype; Heterozygote; Humans; Iran; Mutation; alpha-Globins; alpha-Thalassemia
PubMed: 32072847
DOI: 10.1080/03630269.2019.1694033 -
Journal of Ultrasound in Medicine :... Feb 2015α-Thalassemia prevails in Southeast Asia, where α-thalassemia major is a lethal type. Sonography is a helpful and cost-effective screening tool for detecting... (Review)
Review
α-Thalassemia prevails in Southeast Asia, where α-thalassemia major is a lethal type. Sonography is a helpful and cost-effective screening tool for detecting α-thalassemia major fetuses. The cardiothoracic ratio, placental thickness, and middle cerebral artery peak systolic velocity are most used in clinical practice. These sensitive markers are helpful for evaluation of the hemodynamic status and cardiovascular function of the affected fetuses. They can predict fetal α-thalassemia major and assess the efficacy of treatment noninvasively; therefore, the medical costs as well as the possibility of fetal loss caused by invasive procedures can be reduced. Other potentially useful sonographic markers need further studies, although previous preliminary research suggests their usefulness. This article will review those sonographic markers.
Topics: Biomarkers; Diagnosis, Differential; Female; Humans; Male; Middle Cerebral Artery; Placenta; Pregnancy; Ultrasonography, Prenatal; alpha-Thalassemia
PubMed: 25614392
DOI: 10.7863/ultra.34.2.197 -
Hemoglobin Jan 2022Acknowledging and understanding the extent of thalassemia and hemoglobinopathy issues in a country is crucial for the benefit of implementing a national preventive and... (Review)
Review
Acknowledging and understanding the extent of thalassemia and hemoglobinopathy issues in a country is crucial for the benefit of implementing a national preventive and control program to reduce its prevalence. In order to obtain reliable prevalence data, the gene frequencies of the thalassemias and other hemoglobinopathies should be investigated. Molecular studies on thalassemia have yet to be done for Brunei's population. It was estimated that carriers of thalassemia or hemoglobinopathies in Brunei is approximately 5.0% or less of the overall population. There are about 200 current cases of thalassemia and other hemoglobinopathies including adults and children reported across all four districts of Brunei. Blood parameter analysis, microscopy, hemoglobin (Hb) electrophoresis and high performance liquid chromatography (HPLC) are the most common methods of investigation in aiding diagnosis in the hospital laboratory. Genotyping analysis conducted in an overseas laboratory has been employed to confirm some diagnosis. Compiled data from 2009-2017 at the Hematology Laboratory of the Raja Isteri Pengiran Anak Saleha Hospital, Jalan Putera Al-Muhtadee Billah, Bandar Seri Begawan, Brunei Darussalam, showed that the most reported diagnoses are α-thalassemia (α-thal) trait, β-thalassemia (β-thal) trait, heterozygous Hb E (: c.79G>A)/β-thal, β-thal major (β-TM) and β-thal intermedia (β-TI). The data reported indicate the importance of establishing a thalassemia registry with relevant data on patients and patient outcomes as a tool for monitoring and improving patient care.
Topics: Adult; Brunei; Child; Hemoglobinopathies; Heterozygote; Humans; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950589
DOI: 10.1080/03630269.2021.2008959 -
JPMA. the Journal of the Pakistan... Jan 2021To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening.
OBJECTIVE
To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening.
METHODS
The cross-sectional study was conducted at King Fahad Central Hospital, Jazan, Saudi Arabia, from January 2018 to May 2019, and comprised blood samples of individuals visiting the premarital screening clinic. The samples were analyzed for complete blood counts and haemoglobin electrophoresis. Molecular analysis of samples suspected for alpha thalassemia was done using alpha-globin StripAssay kit. Data was anlaysed using SPSS 20.
RESULTS
Of the 3,970 samples analysed, 1,859(46.83%) were from males and 2,111(53.17%) from females. The overall frequency of suspected alpha thalassemia was 4.43% based upon haematological parameters including complete blood count and haemoglobin electrophoresis. Overall, 80 suspected samples were selected for genetic analyses, and, of them, 76 (95%) were positive for deletional and non-deletional mutations of alpha-globin genes, while 4 (5%) were negative for any of the 21 mutations tested.
CONCLUSIONS
Alpha thalassemia was found to be highly prevalent in the study area.
Topics: Cross-Sectional Studies; Female; Genotype; Humans; Male; Saudi Arabia; alpha-Globins; alpha-Thalassemia
PubMed: 33484530
DOI: 10.47391/JPMA.864 -
Nursing For Women's Health 2016Thalassemia syndromes are becoming more common in the United States as the population becomes more diverse. To provide appropriate care to this patient population,...
Thalassemia syndromes are becoming more common in the United States as the population becomes more diverse. To provide appropriate care to this patient population, nurses must know that thalassemia syndromes are classified into two main types, α-thalassemia and β-thalassemia. α-Thalassemia is further delineated into four clinical patterns: silent carrier state, mild α-thalassemia, hemoglobin H disease, and hydrops fetalis. Understanding each of these complex anemias and their potential effects on a pregnant woman and her fetus will enable nurses to interpret these women's unique laboratory test results. Intervention when necessary with appropriate treatment may lead to optimal outcomes for women and newborns.
Topics: Anemia; Asian; Female; Humans; Infant, Newborn; Pregnancy; Prenatal Diagnosis; Thalassemia; United States; alpha-Thalassemia; beta-Thalassemia
PubMed: 27520605
DOI: 10.1016/j.nwh.2016.07.008 -
American Journal of Hematology Sep 2023This systematic literature review assessed the global prevalence and birth prevalence of clinically significant forms of alpha- and beta-thalassemia. Embase, MEDLINE,...
This systematic literature review assessed the global prevalence and birth prevalence of clinically significant forms of alpha- and beta-thalassemia. Embase, MEDLINE, and the Cochrane Library were searched for observational studies published January 1, 2000, to September 21, 2021. Of 2093 unique records identified, 69 studies reported across 70 publications met eligibility criteria, including 6 records identified from bibliography searches. Thalassemia prevalence estimates varied across countries and even within countries. Across 23 population-based studies reporting clinically significant alpha-thalassemia (e.g., hemoglobin H disease and hemoglobin Bart's hydrops fetalis) and/or beta-thalassemia (beta-thalassemia intermedia, major, and/or hemoglobin E/beta-thalassemia), prevalence estimates per 100 000 people ranged from 0.2 in Spain (over 2014-2017) to 27.2 in Greece (2010-2015) for combined beta- plus alpha-thalassemia; from 0.03 in Spain (2014-2017) to 4.5 in Malaysia (2007-2018) for alpha-thalassemia; and from 0.2 in Spain (2014-2017) to 35.7 to 49.6 in Iraq (2003-2018) for beta-thalassemia. Overall, the estimated prevalence of thalassemia followed the predicted pattern of being higher in the Middle East, Asia, and Mediterranean than in Europe or North America. However, population-based prevalence estimates were not found for many countries, and there was heterogeneity in case definitions, diagnostic methodology, type of thalassemia reported, and details on transfusion requirements. Limited population-based birth prevalence data were found. Twenty-seven studies reported thalassemia prevalence from non-population-based samples. Results from such studies likely do not have countrywide generalizability as they tended to be from highly specific groups. To fully understand the global prevalence of thalassemia, up-to-date, population-based epidemiological data are needed for many countries.
Topics: Pregnancy; Female; Humans; alpha-Thalassemia; beta-Thalassemia; Prenatal Diagnosis; Hydrops Fetalis; Asia; Hemoglobins, Abnormal
PubMed: 37357829
DOI: 10.1002/ajh.27006