Hemoglobin A<sub>2</sub>in Iron Deficient 8-Thalassemia Heterozygotes

Galanello, Renzo; Ruggeri, R; Addis, Maria; Paglietti, E.; Cao, Antonio

doi:10.3109/03630268108991694

Cited by 29 publications

(14 citation statements)

References 3 publications

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“…4) (1). However, there are reports of 8-thalassemia heterozygotes who coinherited triplicated a-globin gene loci (10,11) and, presumably with the greater globin chain imbalance, manifested a more severe clinical syndrome. Four families, of North European descent, came to our attention because of the unusually severe clinical phenotype associated with heterozygous 83-thalassemia.…”

Section: Methodsmentioning

confidence: 96%

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

Thein

Hesketh

Taylor

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

172

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Analysis of the molecular basis of dominantly inherited (3-thalassemia in four families has revealed different mutations involving exon 3 of the (-globin gene. It is suggested that the phenotypic difference between this condition and the more common recessive forms of ,B-thalassemia lies mainly in the length and stability of the abnormal translation products that are synthesized and, in particular, whether they are capable of binding heme and producing aggregations that are relatively resistant to proteolytic degradation. 3924The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Methodsmentioning

confidence: 96%

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

Thein

Hesketh

Taylor

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

172

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“…Associated iron deficiency may result in decreased levels of HbA 2 . This effect, however, is only observed in the presence of severe anemia (Galanello et al 1981). Iron studies can easily exclude this association.…”

Section: Carrier Detectionmentioning

confidence: 97%

The Prevention of Thalassemia

Cao

Kan

2013

Cold Spring Harbor Perspectives in Medicine

208

171

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The thalassemias are among the most common inherited diseases worldwide, affecting individuals originating from the Mediterranean area, Middle East, Transcaucasia, Central Asia, Indian subcontinent, and Southeast Asia. As the diseases require long-term care, prevention of the homozygous state constitutes a major armament in the management. This article discusses the major prevention programs that are set up in many countries in Europe, Asia, and Australia, often drawing from the experience in Sardinia. These comprehensive programs involve carrier detections, molecular diagnostics, genetic counseling, and prenatal diagnosis. Variability of clinical severity can be attributable to interactions with a-thalassemia and mutations that increase fetal productions. Special methods taht are currently quite expensive and not widely applicable are preimplantation and preconception diagnosis. The recent successful studies of fetal DNA in maternal plasma may allow future prenatal diagnosis that is noninvasive for the fetus.

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“…Both conditions are well-known causes of reduced HbA 2 levels. 4,5 Thus, the normal values of HbA 2 are the resultant of factors acting in opposite directions and are only apparent exceptions to the increased HbA2 levels produced by KLF1 mutations. In our cohort of KLF1 heterozygous subjects, known additional mutations previously reported associated with borderline HbA2, such as triplicated ␣-globin genes and/or HBB promoter deletions, were excluded.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Borderline HbA 2 levels associated with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are generally the consequence of mild ␤ ϩ -thalassemia mutations (ie, HBB c.92 ϩ 6 T 3 C), coinherited ␦ and ␤-thalassemia, ␤-promoter mutations Ϫ92 (HBB c.-142 C 3 T), or coexisting iron deficiency anemia. [1][2][3][4][5] Borderline HbA 2 with normal MCV and MCH may be an outlier value of the normal HbA 2 distribution in the noncarrier population or the effect of genetic determinants able to increase HbA 2 levels. The genetic determinants so far identified are the triplication of the ␣-globin genes, ␤-promoter mutations (HBB c.-151 C 3 T), and some HBD and HBB gene variants.…”

Section: Introductionmentioning

confidence: 99%

KLF1 gene mutations cause borderline HbA2

Perseu

Satta

Moi

et al. 2011

Blood

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Increased hemoglobin A 2 (HbA 2 ; ie, levels > 3.9%) is the most important feature of-thalassemia carriers. However, it is not uncommon to find persons with borderline HbA 2 (levels, 3.3%-3.8%), who pose a relevant screening problem. Several genotypes have been associated with borderline HbA 2 , but sometimes the reasons for this unusual phenotype are unknown. In this paper, we report, for the first time, that mutations of KLF1 result in HbA 2 levels in the borderline range. Six different KLF1 mutations were identified in 52 of 145 subjects with borderline HbA 2 and normal mean corpuscular volume and mean corpuscular hemoglobin. Two mutations (T327S and T280_H283del) are here reported for the first time. The prevalent mutation in Sardinians is S270X, which accounts for 80.8% of the total. The frequent discovery of KLF1 mutations in these atypical carriers may contribute significantly to the thalassemia screening programs aimed at identification of at risk couples. (Blood. 2011;118(16): 4454-4458)

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Hemoglobin A₂in Iron Deficient 8-Thalassemia Heterozygotes

Cited by 29 publications

References 3 publications

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

The Prevention of Thalassemia

KLF1 gene mutations cause borderline HbA2

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Hemoglobin A2in Iron Deficient 8-Thalassemia Heterozygotes

Cited by 29 publications

References 3 publications

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

The Prevention of Thalassemia

KLF1 gene mutations cause borderline HbA2

Contact Info

Product

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Hemoglobin A₂in Iron Deficient 8-Thalassemia Heterozygotes