Genotype-Phenotype Relationship of the δ-Thalassemia and Hb A 2 Variants: Observation of 52 Genotypes
2010; Taylor & Francis; Volume: 34; Issue: 5 Linguagem: Inglês
10.3109/03630269.2010.511586
ISSN1532-432X
AutoresGiuseppina Lacerra, Clelia Scarano, Laura F. Lagona, Rosario Testa, Daniela Caruso, Emilia Medulla, Maria G. Friscia, Lucia Mastrullo, Mercedes Caldora, Romeo Prezioso, Carlo Gaudiano, Carmelo Magnano, M. A. Romeo, Gennaro Musollino, Francesca Di Noce, Clementina Carestia,
Tópico(s)Neonatal Health and Biochemistry
ResumoThe increase of Hb A2 (α2δ2) beyond the upper limit [2.0–2.2/3.3–3.4% of the total hemoglobin (Hb)] is an invaluable tool in the hematological screening of β-thalassemia (β-thal) carriers. Factors decreasing Hb A2 percentages can hinder correct diagnosis. In order to analyze the genotype-phenotype relationship, we characterized δ-, β- and α-globin genotypes in 190 families where the probands had Hb A2 values of ≤2.0% or were β-thal heterozygotes with normal Hb A2 levels. Hb A2 was measured with cation exchange high performance liquid chromatography (HPLC). Mutations were detected with allele-specific methods or DNA sequencing; two multiplex-ARMS (amplification refractory mutation system) assays were set up. The molecular basis underlying the decrease in Hb A2 was extremely heterogeneous. Nineteen δ-globin alleles (Hb A2-S.N. Garganico was new) were detected; their interaction with α- or β-globin alleles (10 and eight, respectively) led us to observe 52 genotypes in 261 carriers. The type of δ-globin mutations, the relative genotypes, the interaction with α0-thal traits, are the most important factors in decreasing the Hb A2 percentage. These results are extremely useful in addressing the molecular diagnosis of hemoglobinopathies and thalassemias.
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