title: HbH disease in Sardinia: molecular, hematological and clinical aspects.
abstract: In this study we have defined the molecular basis and correlated the clinical phenotype with the alpha-globin genotype in a large series of patients of Sardinian descent with HbH disease. The most prevalent molecular defect was the deletion of 3 alpha-globin structural genes most commonly the (--/-alpha 3.7) genotype (83.6%) and rarely the (--/-alpha 4.2) genotype (1.4%), followed in decreasing order of incidence by the combination of deletion alpha zero-thalassemia and initiation codon mutation of the alpha 2-gene (--/alpha NcoI alpha = 9.8%), deletion alpha zero-thalassemia and pentanucleotide deletion of IVS-I of the alpha 2-globin gene, (--/alpha HphI alpha = 3.3%) deletion alpha zero-thalassemia and initiation codon mutation of the alpha 1-gene (--/alpha alpha NcoI = 1.3%), a homozygous state for initiation codon mutation of the alpha 2-gene (alpha Nco alpha/alpha NcoI alpha = 0.7%). Patients with the (--/alpha thal alpha) genotypes showed severer clinical and hematological features as compared to those with the (--/-alpha) or those with the (--/alpha alpha thal) genotypes. The single patient with the (alpha Nco alpha/alpha Nco alpha) genotype had a clinical phenotype intermediate between HbH disease and the alpha-thalassemia carrier status. This heterogeneity depends on the fact that the alpha 2-globin gene produces 2-3 times alpha-globin chains than the alpha 1-gene and the single remaining alpha 1-like globin gene in the -alpha 3.7 chromosome has a compensatory increase in the alpha-globin chain output. alpha-Globin gene mapping of HbH disease patients may be useful for predicting the clinical outcome and to improve genetic counseling.
authors.affiliation: Istituto di Clinica e Biologia dell'età Evolutiva, Università degli Studi di Cagliari, Italia.
authors.forename: R
authors.initials: R
authors.lastname: Galanello
authors.forename: B
authors.initials: B
authors.lastname: Aru
authors.forename: C
authors.initials: C
authors.lastname: Dessì
authors.forename: M
authors.initials: M
authors.lastname: Addis
authors.forename: E
authors.initials: E
authors.lastname: Paglietti
authors.forename: M A
authors.initials: MA
authors.lastname: Melis
authors.forename: S
authors.initials: S
authors.lastname: Cocco
authors.forename: P
authors.initials: P
authors.lastname: Massa
authors.forename: N
authors.initials: N
authors.lastname: Giagu
authors.forename: S
authors.initials: S
authors.lastname: Barella
mesh_terms: D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D017353:Gene Deletion; D005796:Genes; D005838:Genotype; D005914:Globins / Q000235:genetics; D006447:Hemoglobin H / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007558:Italy; D010641:Phenotype
chemical_list: D005914:Globins; D006447:Hemoglobin H