Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (α<sup>T-Saudi</sup>α) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses

Moamen, Nabeel J. Al; Ahmed, Thabet; Mahdi, F.; Newton, Hema; Salman, Ebtihal

doi:10.1080/03630269.2018.1499523

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…Another recent study reported on an additional 44 cases (Shamoon et al 2020), and if the molecular results from these 55 cases are pooled together, the most frequent genotype would be −α 3.7 /-MED documented in 67.3%, followed by α PolyA1 α/α PolyA1 α, and −α 4.2 /-MED in 10.9% and 5.4%, respectively. These observations are more or less consistent with reports from Turkey and Iran where −α 3.7 /-MED is the most frequent genotype associated with Hb H disease (Cürük 2007;Paridar et al 2019), but are strikingly different from reports from Saudi Arabia and other Peninsular Arab countries where the main genotype associated with Hb H is α PolyA1 α/α PolyA1 α (Adekile et al 1994;Al-Awamy 2000;Al-Riyami et al 2020;Al Moamen et al 2018).…”

Section: Molecular Basis Of Alpha Thalassemia Among Iraqi Kurdssupporting

confidence: 84%

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

2020

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Hemoglobinopathies are major health problems among Iraqi Kurds, who are a distinct ethnic group inhabiting North and Northeastern Iraq. We reviewed published literature on these disorders in this part of the world, and it was revealed that the most prevalent is β-thalassemia with carrier rates of 3.7-6.9%. Alpha thalassemia is less prevalent with carrier rates of 0.03-1.22%, while the sickle cell gene is variably distributed with carrier rates of 0.06-1.2%. Other structural hemoglobinopathies and δβ-thalassemia are sporadic. Twenty-seven different β-thalassemia mutations were identified, with seven constituting 82% of 1039 chromosomes characterized, namely: IVS-II-1 (G>A), IVS-I-6 (T>C), IVS-I-I (G>A), codon 8 (−AA), codon 8/9 (+G), IVS-I-110 (G>A), and codon 5 (-CT). There were notable regional variations in the distribution of β-thalassemia mutations, with Cd44 being mainly prevalent in the North, while IVS-I-110 is mainly prevalent in the East. In relevance to α-thalassemia, ten different mutations were detected, with the four most frequent constituting 92.4% of 262 alleles characterized being: −α 3.7 , -MED , α −5nt α, and α PolyA1 α. In relevance to sickle cell gene, it is seen in the northern part of the region bordering Turkey, with comparable prevalence rates, and is associated, similar to Turkey, mainly with the Benin haplotype, unlike that in Southern Iraq where it is associated with the Arab-Indian haplotype, similar to Eastern Arabian Peninsula. Given the high prevalence of hemoglobinopathies in the region, and the high rates of consanguineous marriages, a preventive program was initiated in 2008, and results of its first 5 years were promising, though there are still many outstanding challenges that require addressing.

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Section: Molecular Basis Of Alpha Thalassemia Among Iraqi Kurdssupporting

confidence: 84%

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

2020

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“…On the other hand, when HbH disease is inherited with sickle cell trait (β-gene mutation) may produce hemolytic anemia with decreased or non-detectable β-globin tetramers HbH. The HbH percentage of our patient was 5.2% in contrast with higher HbH levels, approximately 20%-30%, in patients with HbH disease without the coinheritance of the HbS trait (Figure 2B), while in the study of Al Moamen et al HbH ranged from 7.5% to 27.5% in the specific alpha genotype [2]. The reason is that there are decreased β A -globin chains available for HbH formation since only the non-mutant β-globin gene synthesizes these chains.…”

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confidence: 57%

“…αΤSaudi homozygosity is linked to HbH clinical phenotype, despite that only two out of four α‐genes are affected. The severity of the specific mutation is proposed to be due to a transcriptional interference mechanism leading to the structurally normal α1‐globin gene downregulation [ 2 ]. The above‐mentioned lower HbH quantity could lead to a milder type of HbH disease with less ineffective hematopoiesis and therefore reduced iron overload (our patient had no iron overload) [ 5 ].…”

Section: Figurementioning

confidence: 99%

Coinheritance of non‐deletional hemoglobin H disease with sickle cell trait

Komninaka,

Ntelaki

2024

eJHaem

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“…In other studies, the prevalence of α + thalassemia trait ranged from 15% to 20% [4,5]. Thus, −α 3.7 is the most common variant in the region, while the non-deletional variant HBA2:c.*94A>G is less frequent [6][7][8].…”

Section: Introductionmentioning

confidence: 88%

Premarital Counseling on the Alpha Thalassemia Allele HBA2:c.*94A>G

Alderei,

Alshkeili,

Alnaqbi

et al. 2024

Thalassemia Reports

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The mutation HBA2:c.*94A>G (AATAAA>AATAAG; rs63751269) is a 3′-UTR (3 prime untranslated region) single-nucleotide substitution in the polyadenylation (PA) signal of HBA2 (αPA:A→G). This pathogenic (CADD score, 14.92) variant is sporadic in the Arabian Peninsula. It results in inefficient mRNA processing, transcription termination, and possibly using an alternate cryptic downstream polyadenylation signal. As a result, the allele αT (or αT-Saudi) poses challenges in premarital counseling with respect to fetal risk of hemoglobin H disease. Homozygous HBA2:c.*94A>G (αTα/αTα) results in moderate-to-severe microcytosis (mean red cell volume, MCV, 55 to 65 fL), reflecting markedly impaired hemoglobin synthesis (hemoglobin H disease). Homozygous rightward -α3.7 (a 3804-neocleotide deletion allele, NM_000517.4:c.[-2_-3delAC; −α3.7]), on the other hand, results in mild microcytosis (MCV, 70 to 75 fL, alpha-thalassemia trait). Thus, HBA2:c.*94A>G is more damaging than -α3.7. Consistently, the value of MCV in compound heterozygosity, HBA2:c.*94A>G and −α3.7, is 65 to 70 fL. We report here a healthy couple who presented for premarital counseling on their hemoglobinopathy. The man has homozygous HBA2:c.*94A>G (αTα/αTα), and the woman has compound heterozygous (−α3.7/αTα, also annotated as: −3.7α/αTα). As a result, the genotype of their offspring would be that of the father (αTα/αTα) or the mother (−α3.7/αTα). The counseling was mainly based on the benign phenotypes of the parents. As both were asymptomatic and their anemia was clinically insignificant, they proceeded with the marriage.

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Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (α^T-Saudiα) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses

Cited by 7 publications

References 19 publications

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

Coinheritance of non‐deletional hemoglobin H disease with sickle cell trait

Premarital Counseling on the Alpha Thalassemia Allele HBA2:c.*94A>G

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Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (αT-Saudiα) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses

Cited by 7 publications

References 19 publications

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

Coinheritance of non‐deletional hemoglobin H disease with sickle cell trait

Premarital Counseling on the Alpha Thalassemia Allele HBA2:c.*94A>G

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Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (α^T-Saudiα) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses