Different hematologic phenotypes are associated with the leftward (-alpha 4.2) and rightward (-alpha 3.7) alpha+-thalassemia deletions.

Bowden, Donald Keith; Hill, Adrian V. S.; Higgs, Douglas R.; Oppenheimer, Stephen; Weatherall, D. J.; Clegg, J. B.

doi:10.1172/jci112804

Cited by 46 publications

(24 citation statements)

References 29 publications

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“…This distinction in allele frequency observed amongst ethnic Chinese consolidates our previous finding [7] and is in accordance with the findings of other similar studies on the local population [11]. In general, the α – 3.7 single gene deletion has a global distribution among all ethnic groups, and is especially prevalent in most tropical and subtropical populations studied [12]. …”

Section: Resultssupporting

confidence: 91%

Distribution of Alpha Thalassaemia Gene Variants in Diverse Ethnic Populations in Malaysia: Data from the Institute for Medical Research

Ahmad

Saleem

Aloysious

et al. 2013

IJMS

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Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, – – SEA, – – THAI, ––FIL; two single-gene deletions, α–3.7 and – α4.2; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong Sze) and Cd142 (Hb Constant Spring). A high incidence of α–3.7 deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the – – SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α–3.7 deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α+ thalassaemia traits, 973 heterozygous α0 thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective.

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Section: Resultssupporting

confidence: 91%

Distribution of Alpha Thalassaemia Gene Variants in Diverse Ethnic Populations in Malaysia: Data from the Institute for Medical Research

Ahmad

Saleem

Aloysious

et al. 2013

IJMS

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“…In this context, it should be noted that heterozygotes for nondeletion defects usually manifested the «-thalassemia carrier phenotype, whereas persons with a single a-globin gene deletion have either silent carrier phenotype or ex press very mild thalassemia-like hematological manifes tations [19,20]. These findings may be explained on the ba sis of recent studies which demonstrated that: (a) the « 2-globin gene produces 2-3 times more a-globin chains as compared to the «r globin gene [21], and (b) the remaining a-globin gene in the rightward deletion (-a 3-7), but not in the leftward (-a 4,2), shows a compensatory increase around 1.8 times of the a-globin chain output [22][23][24]. Fur thermore a-globin production during in vitro translation of reticulocyte RNA and during labelling of intact reticu locytes was less significantly depressed in HbH disease pa tients with a combination of a deletion defect and an ini tiation codon mutation of the a,-gene than in the patients with a similar initiation codon mutation (a ,hala) of the a 2- gene [18].…”

Section: Discussionmentioning

confidence: 99%

HbH Disease in Sardinia: Molecular, Hematological and Clinical Aspects

et al. 1992

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In this study we have defined the molecular basis and correlated the clinical phenotype with the α-globin genotype in a large series of patients of Sardinian descent with HbH disease. The most prevalent molecular defect was the deletion of 3 α-globin structural genes most commonly the (– –/–α^3.7) genotype (83.6%) and rarely the (– –/– α^4.2) genotype (1.4%), followed in decreasing order of incidence by the combination of deletion α°-thalassemia and initiation codon mutation of the α₂-gene (– –/α^NcoIα = 9.8%), deletion α°-thalassemia and pentanucleotide deletion of IVS-I of the α₂-globin gene, (– –/α^HphIα = 3.3%) deletion α°-thalassemia and initiation codon mutation of the α₁-gene (– –/αα^NcoI = 1.3%), a homozygous state for initiation codon mutation of the α₂-gene (α^Ncoα/α^NcoIα = 0.7%). Patients with the (– –/α^thalα) genotypes showed severer clinical and hematological features as compared to those with the (– –/–α) or those with the (– –/αα^thal) genotypes. The single patient with the (α^Ncoα/α^Ncoα) genotype had a clinical phenotype intermediate between HbH disease and the α-thalassemia carrier status. This heterogeneity depends on the fact that the α₂-globin gene produces 2-3 times α-globin chains than the α₁-gene and the single remaining α₁-like globin gene in the -α^{3 7} chromosome has a compensatory increase in the α-globin chain output. α-Globin gene mapping of HbH disease patients may be useful for predicting the clinical outcome and to improve genetic counselling.

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“…Such a phenomenon is not demonstrated in the –α 4.2 kb deletion [5, 6]. Deletional α-thals are more common than the nondeletional types.…”

Section: Introductionmentioning

confidence: 99%

α-Thalassemia in the United Arab Emirates

El-Kalla

Baysal²

1998

Acta Haematol

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A neonatal screening survey of α-thalassemia (α-thal) among the United Arab Emirates (UAE) nationals was conducted on 418 consecutive cord blood samples. Our findings demonstrate that 49% of the cases studied were found with an α-globin gene defect. The gene frequency of the –α^3.7 was 0.2847 and that of the –α^4.2 was 0.0072. Four nondeletional α-thal mutations were found; α^PA-1, α^PA-2, Hb CS and α^-5nt del with gene frequencies of 0.0036, 0.0012, 0.0024, and 0.0072, respectively. We also report here the genotype-phenotype correlation in 22 patients with Hb H disease or Hb H-like syndrome. Of these, 6 were homozygous for the α^PA-1 mutation, 2 were homozygous for Hb CS, and 14 were compound heterozygous for either α^PA-1, Hb CS, α^-5nt del or ––MED-I, with the –α^3.7. The data reported here demonstrate that a considerable heterogeneity of α-thal mutations occurs in the UAE and that the incidence of α-thal in the indigenous population is one of the highest in the world. Our clinical data suggest that Hb H disease in the UAE has, in general, a mild to moderate phenotypic presentation.

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Different hematologic phenotypes are associated with the leftward (-alpha 4.2) and rightward (-alpha 3.7) alpha+-thalassemia deletions.

Cited by 46 publications

References 29 publications

Distribution of Alpha Thalassaemia Gene Variants in Diverse Ethnic Populations in Malaysia: Data from the Institute for Medical Research

Distribution of Alpha Thalassaemia Gene Variants in Diverse Ethnic Populations in Malaysia: Data from the Institute for Medical Research

HbH Disease in Sardinia: Molecular, Hematological and Clinical Aspects

α-Thalassemia in the United Arab Emirates

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