title: The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia.
abstract: 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.
  
  
  
  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.
  
  
  
  Various β-globin mutations and KLF1 gene defects are the most common genetic determinants responsible for this phenotype in our population.
  
  
  
  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.
authors.affiliation: Dipartimento di Sanitx00E0; Pubblica, Medicina Clinica e Molecolare, Universitx00E0; degli Studi di Cagliari, Ospedale Microcitemico, Cagliari, Italy.
authors.forename: Maria Elisabetta
authors.initials: ME
authors.lastname: Paglietti
authors.forename: Stefania
authors.initials: S
authors.lastname: Satta
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Sollaino
authors.forename: Susanna
authors.initials: S
authors.lastname: Barella
authors.forename: Arianna
authors.initials: A
authors.lastname: Ventrella
authors.forename: Maria Franca
authors.initials: MF
authors.lastname: Desogus
authors.forename: Franca Rosa
authors.initials: FR
authors.lastname: Demartis
authors.forename: Laura
authors.initials: L
authors.lastname: Manunza
authors.forename: Raffaella
authors.initials: R
authors.lastname: Origa
mesh_terms: D006443:Hemoglobin A2 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000175:diagnosis*
chemical_list: D055542:alpha-Globins; D055544:beta-Globins; D006443:Hemoglobin A2