title: Genotype-phenotype relationship of the δ-thalassemia and Hb A(2) variants: observation of 52 genotypes.
abstract: The increase of Hb A(2) (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 A(2) 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 A(2) values of ≤2.0% or were β-thal heterozygotes with normal Hb A(2) levels. Hb A(2) 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 A(2) was extremely heterogeneous. Nineteen δ-globin alleles (Hb A(2)-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 α(0)-thal traits, are the most important factors in decreasing the Hb A(2) percentage. These results are extremely useful in addressing the molecular diagnosis of hemoglobinopathies and thalassemias.
authors.affiliation: Istituto di Genetica e Biofisica Adriano Buzzati-Traverso, CNR, Napoli, Italia. lacerra@igb.cnr.it
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lacerra
authors.forename: Clelia
authors.initials: C
authors.lastname: Scarano
authors.forename: Laura F
authors.initials: LF
authors.lastname: Lagona
authors.forename: Rosario
authors.initials: R
authors.lastname: Testa
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Caruso
authors.forename: Emilia
authors.initials: E
authors.lastname: Medulla
authors.forename: Maria G
authors.initials: MG
authors.lastname: Friscia
authors.forename: Lucia
authors.initials: L
authors.lastname: Mastrullo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Caldora
authors.forename: Romeo
authors.initials: R
authors.lastname: Prezioso
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaudiano
authors.forename: Carmelo
authors.initials: C
authors.lastname: Magnano
authors.forename: Maria A
authors.initials: MA
authors.lastname: Romeo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Musollino
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Noce
authors.forename: Clementina
authors.initials: C
authors.lastname: Carestia
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis / Q000379:methods; D017931:DNA Primers; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006443:Hemoglobin A2 / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D055546:delta-Globins / Q000235:genetics; D055538:delta-Thalassemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
chemical_list: D017931:DNA Primers; D055542:alpha-Globins; D055544:beta-Globins; D055546:delta-Globins; D006443:Hemoglobin A2