Hb H disease resulting from the association of an αº-thalassemia allele [-(α)20.5] with an unstable α-globin variant [Hb Icaria]: first report on the occurrence in Brazil

Kimura, Elza; Oliveira, De; Fertrin, Kleber Yotsumoto; Pinheiro, Valéria Rosado; Jorge, Susan E.; Costa, Fernando Ferreira; Sonati, María de Fátima

doi:10.1590/s1415-47572009005000071

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…In this case, the elongated and unstable alpha-chain in association with the −(α) 20.5 deletion, resulted in Hb H disease with high levels of Hb H and Hb Bart's (14.7% and 19.0%, respectively) ( Table 2 ). 4 …”

Section: Resultsmentioning

confidence: 99%

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Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

Kimura

Oliveira

Jorge

et al. 2015

Revista Brasileira de Hematologia e Hemoterapia

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BackgroundBrazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population.MethodsA total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme–heme cooperativity and Bohr effect of the variants were evaluated by functional tests.ResultsFour new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia.ConclusionThe variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.

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Section: Resultsmentioning

confidence: 99%

“…3 In addition, there are elongated and extremely unstable variants that lead to thalassemia phenotypes. 4 …”

Section: Introductionmentioning

confidence: 99%

Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

Kimura

Oliveira

Jorge

et al. 2015

Revista Brasileira de Hematologia e Hemoterapia

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“…Further molecular methods such as mismatched-PCR-RFLP (11) or reverse dot-blot (5) or sequencing (12) may be performed subsequently in order to distinguish between these different mutations. However, as most of the above mentioned mutations may cause severe anemia (13,14), this simple method could be valuable in premarital screening to find couples at-risk of having severely anemic children. Moreover, as previous studies using reverse dot-blot or sequencing methods revealed mostly the presence of Hb CS and rare cases of Hb Icaria (5)(6)(7)12) in the Iranian population, we assumed that those alleles which remained uncut at the termination codon while using the Tru9I restriction enzyme in this study, corresponded to Hb CS.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Detection of Hb Constant Spring (α142, TAA>CAA, α2) and The α2 IVS-I Donor Site (−TGAGG) Deletion by a Simple Polymerase Chain Reaction-Based Method in Iran

et al. 2012

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Hb Constant Spring (Hb CS, codon 142, TAA>CAA, α2) (HBA2:c.427T>C) and α2 IVS-I donor site (GAGGTGAGG>GAGG - - - - -) (HBA2:c.95+2_95+6delTGAGG) are nondeletional α-thalassemia (α-thal) mutations found all over the world. Identification of α-thal genotypes in at-risk couples for severe anemia or in highly heterogeneous populations requires rapid, accurate and cost-effective genotyping methods. In this study, a pair of primers were used to specifically amplify an 883 bp fragment from the α2-globin gene in order to simultaneously identify these two mutations by a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. We determined the genotypic frequencies of Hb CS and the α2 IVS-I donor site mutations after amplification and enzymatic digestion with Tru9I in 238 northern Iranian samples referred for α-thal testing. Hb CS and the α2 IVS-I donor site mutations accounted for 21 (8.8%) and 29 (12.2%) of the nondeletional cases. This genotyping assay has proven to be a rapid, reliable and useful diagnostic tool for simultaneous detection of these two anomalies for genetic counseling or further prenatal diagnosis.

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“…In Brazil, its prevalence is high ( Sonati et al , 1991 ; Couto et al , 2003 ; Adorno et al , 2005 ; Wagner et al , 2010 ; Cardoso et al , 2012 ; De Medeiros Alcoforado et al , 2012 ). However, Hb H disease, which is found primarily in Southeast Asia, the Middle East and the Mediterranean, has only rarely been reported in Brazil, where most cases are the result of an interaction of the -α 3.7 deletion with the -- MED , -(α) 20.5 , or -- SEA deletions ( Sonati et al , 1992 ; Wenning et al , 2000 , 2002 , 2009 ; Kimura et al , 2009 ). Combinations of the -α 3.7 deletion with new or rare α 0 deletions started to be detected in the Brazilian population more recently, suggesting that the prevalence of Hb H disease may be underestimated ( Suemasu et al , 2011 ).…”

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Rare α0-thalassemia deletions detected by MLPA in five unrelated Brazilian patients

et al. 2017

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Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability, ranging from a practically asymptomatic phenotype to severe anemia, which can lead to intrauterine or early neonatal death. Deletions affecting the α-globin genes, located on chromosome 16p13.3, are the main causes of α-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause α-thalassemia, particularly large deletions involving the whole α cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of α-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -α3.7 deletion identified in the patients with Hb H disease, four different α0 deletions removing 15 to 225 kb DNA segments were found: two of them remove both the α genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire α cluster and the HS-40 region. These results illustrate the diversity of α-thalassemia deletions in the Brazilian population and highlight the importance of molecular investigation in cases that present with microcytosis and hypochromia without iron deficiency and normal or reduced Hb A2 levels..

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Hb H disease resulting from the association of an αº-thalassemia allele [-(α)20.5] with an unstable α-globin variant [Hb Icaria]: first report on the occurrence in Brazil

Cited by 3 publications

References 14 publications

Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

Simultaneous Detection of Hb Constant Spring (α142, TAA>CAA, α2) and The α2 IVS-I Donor Site (−TGAGG) Deletion by a Simple Polymerase Chain Reaction-Based Method in Iran

Rare α0-thalassemia deletions detected by MLPA in five unrelated Brazilian patients

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