title: Role of polymorphic sequences 5' to the G(gamma) gene and 5' to the beta gene on the homozygous beta thalassemic phenotype.
abstract: Sixty-seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their beta-thalassemia (thal) mutations. We investigated whether some co-inherited genetic factors could influence the phenotype. Patients with milder beta-thal defects, homozygotes or compound heterozygotes for the IVS-I-6 (T-->C) or -87 (C-->G) mutations had a milder disease. In addition, determination of the co-inheritance of the -158 (C-->T) G(gamma) polymorphism and the (AT)9T5 repeat motif in the region -540 to -525, 5' to the beta-globin gene, showed that in some patients with severe or mild/severe beta-thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous beta-thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the -158 (C-->T) G(gamma) and (AT)9T5 repeat motif, increasing the Hb F expression and ameliorate the clinical course of the disease.
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy. mara.ferrara@unina2.it
authors.forename: Mara
authors.initials: M
authors.lastname: Ferrara
authors.forename: Sofia M R
authors.initials: SM
authors.lastname: Matarese
authors.forename: Matteo
authors.initials: M
authors.lastname: Francese
authors.forename: Barbara
authors.initials: B
authors.lastname: Borrelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Perrotta
authors.forename: Anna
authors.initials: A
authors.lastname: Meo
authors.forename: Maria A
authors.initials: MA
authors.lastname: La Rosa
authors.forename: Luigi
authors.initials: L
authors.lastname: Esposito
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin