α-Globin Gene Quadruplication and Heterozygous β-Thalassemia: A Not So Rare Cause of Thalassemia Intermedia

Origa, Raffaella; Sollaino, Maria Carla; Borgna‐Pignatti, Caterina; Piga, Antonio; Torres, Aurora Feliú; Masile, Valentina; Galanello, Renzo

doi:10.1159/000353410

Cited by 18 publications

(16 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding is in agreement with our previous data showing that some patients with the triplication/quadruplication of α-globin genes and no heterozygosity of β-thalassemia can show a hematologically silent phenotype and a normal or borderline level of HbA2 [16,17,18]. However, given the limited data on the hematological phenotypes associated with these rearrangements in the literature, the search for these determinants should be performed.…”

Section: Resultssupporting

confidence: 91%

“…The search of KLF1 mutations and of additional α-globin genes was not performed in subjects found to be β-thalassemia heterozygous because the levels of HbA2 were not unusually high [7,10] and they presented with a normal clinical phenotype [17,18]. The investigation of additional α-globin genes was instead performed in subjects who were positive for a KLF1 mutation because double heterozygosity of both these genetic determinants has not been described and the resulting hematological phenotypes are not known.…”

Section: Resultsmentioning

confidence: 99%

“…These factors, when interacting with the classic β-thalassemia trait, may result in a variable thalassemia intermedia phenotype [1,3,15,16,17,18]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background: The increase in HbA2 is the most important parameter for the identification of thalassemia carriers. However, in routine screening for hemoglobinopathies, some cases are difficult to classify because the level of HbA2 is not typically elevated. In this work, we report the results of a molecular investigation on a cohort of subjects with borderline HbA2. Methods: All subjects with a β-thalassemia carrier partner and a borderline percentage level of HbA2 were investigated for the presence of a pathological mutation in the β-globin gene. All negative subjects were screened for both the KLF1 mutation and the presence of ααα/ or αααα/ alleles. The subjects with reduced MCV and/or MCH were also screened for deletional and nondeletional α-globin gene defects. Results: Various β-globin mutations and KLF1 gene defects are the most common genetic determinants responsible for this phenotype in our population. Conclusion: KLF1 mutations are important in a screening program for hemoglobinopathies. An increase in HbF in association with borderline HbA2 levels is a useful but not exclusive marker that suggests the investigation of this gene. On the basis of our findings, we are able to suggest the molecular procedure to use in a population characterized by a high prevalence of thalassemia carriers.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Contrary to the beneficial effect demonstrated by coinheritance of a-and b-thalassemia, inheritance of excess a-globin genes worsens the a-like/b-like globin chain imbalance and results in a more severe clinical phenotype. [67][68][69] This observation further emphasizes that the number of functional a-globin genes has a clear direct effect on the clinical severity of patients with b-thalassemia. …”

Section: Coinheritance Of A-and B-thalassemiamentioning

confidence: 74%

α-Globin as a molecular target in the treatment of β-thalassemia

Mettananda

Gibbons

Higgs

2015

Blood

127

120

View full text Add to dashboard Cite

The thalassemias, together with sickle cell anemia and its variants, are the world’s most common form of inherited anemia, and in economically undeveloped countries, they still account for tens of thousands of premature deaths every year. In developed countries, treatment of thalassemia is also still far from ideal, requiring lifelong transfusion or allogeneic bone marrow transplantation. Clinical and molecular genetic studies over the course of the last 50 years have demonstrated how coinheritance of modifier genes, which alter the balance of α-like and β-like globin gene expression, may transform severe, transfusion-dependent thalassemia into relatively mild forms of anemia. Most attention has been paid to pathways that increase γ-globin expression, and hence the production of fetal hemoglobin. Here we review the evidence that reduction of α-globin expression may provide an equally plausible approach to ameliorating clinically severe forms of β-thalassemia, and in particular, the very common subgroup of patients with hemoglobin E β-thalassemia that makes up approximately half of all patients born each year with severe β-thalassemia.

show abstract

“…There are many reports about the phenotypic variability of β-thalassemia carriers in association with an increasing number of α genes. This variability goes from mild to severe thalassemia intermedia [10][11][12][13]. In a previous study, we describe a child with the same β-thalassemia mutation IVS2-654 (C→T) and a full duplicated α-globin gene cluster (391 kb), but presenting with a transfusion-dependent phenotype since the age of 4 months [14].…”

Section: Discussionmentioning

confidence: 96%

Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child

Jiang

et al. 2015

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

Thalassemia intermedia is an inherited hemoglobin disorder characterized by a significant genetic and clinical heterogeneity. A wide spectrum of different genotypes-homozygous, heterozygous, and compound heterozygous-have been found to be responsible for it. The authors describe a Chinese child of β-thalassemia heterozygote with the mutation IVS2-654 (C→T) (HBB:c.316-197C→T) presenting with severe thalassemia intermedia. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α gene cluster revealed an approximate 146-kb duplication at 16p13.3 including the complete α gene cluster. The duplicated allele and the normal allele in trans result in a total of 6 active α genes. The severe clinical phenotype seemed to be related to the considerable excess of the α-globin and the β-globin deficit caused by the presence of the β-thalassemia. The α gene duplication should be considered in patients heterozygous for β-thalassemia who show a more severe phenotype than β-thalassemia trait.

show abstract

α-Globin Gene Quadruplication and Heterozygous β-Thalassemia: A Not So Rare Cause of Thalassemia Intermedia

Cited by 18 publications

References 14 publications

The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia

The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia

α-Globin as a molecular target in the treatment of β-thalassemia

Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child

Contact Info

Product

Resources

About