title: Complexity of the alpha-globin genotypes identified with thalassemia screening in Sardinia.
abstract: α-Thalassemia commonly results from deletions or point mutations in one or both α-globin genes located on chromosome 16p13.3 giving rise to complex and variable genotypes and phenotypes. Rarely, unusual non-deletion defects or atypical deletions down-regulate the expression of the α-globin gene. In the last decade of the program for β-thalassemia carrier screening and genetic counseling in Sardinia, the association of new techniques of molecular biology such as gene sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) to conventional methods has allowed to better define several thalassemic genotypes and the complex variability of the α-cluster with its flanking regions, with a high frequency of different genotypes and compound heterozygosity for two α mutations even in the same family. The exact molecular definition of the genotypes resulting from the interactions among the large number of α-thalassemia determinants and with β-thalassemia, is important for a correct correlation of genotype-phenotype and to prevent underdiagnosis of carrier status which could hamper the effectiveness of a screening program particularly in those regions where a high frequency of hemoglobinopathies is present.
authors.affiliation: Clinica Pediatrica 2°, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare, Università di Cagliari, Ospedale Regionale per le Microcitemie, ASL 8 Cagliari, Italy. Electronic address: secondacasella@hotmail.com.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Origa
authors.forename: Maria E
authors.initials: ME
authors.lastname: Paglietti
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sollaino
authors.forename: Maria F
authors.initials: MF
authors.lastname: Desogus
authors.forename: Susanna
authors.initials: S
authors.lastname: Barella
authors.forename: Daniela
authors.initials: D
authors.lastname: Loi
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
mesh_terms: D000483:Alleles; D002353:Carrier State; D002885:Chromosomes, Human, Pair 16; D005787:Gene Frequency; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007558:Italy; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D055542:alpha-Globins
keywords: Additional alpha globin genes; Alpha thalassemia; Compound heterozygosity; Hb-variants