title: Somatic deletion of the normal beta-globin gene leading to thalassaemia intermedia in heterozygous beta-thalassaemic patients.
abstract: Two beta-thalassaemia patients, whose constitutive genotype was beta(39C)/beta(39C-->T), had the clinical phenotype beta-thalassaemia intermedia. Analysis of leucocyte DNA showed the presence of the mutated beta(39C-->T)-gene exclusively, while the normal beta(39C)-gene was also present in reticulocyte RNA. Deletional analysis of chromosome 11p15.5 on leucocyte DNA showed large deletions including the beta-globin gene. Two populations of erythroid progenitors, one heterozygous and the other hemizygous for the beta(39C-->T) mutation, were demonstrated in one case. This confirms that, in heterozygous individuals, beta-thalassaemia intermedia may be caused by inactivation of the beta-locus in trans as a result of chromosome 11p15.5 deletions in a subpopulation of haematopoietic cells.
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Ospedale Microcitemico, University of Cagliari, 09121 Cagliari, Italy. renzo.galanello@mcweb.unica.it
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Lucia
authors.initials: L
authors.lastname: Perseu
authors.forename: Chiara
authors.initials: C
authors.lastname: Perra
authors.forename: Liliana
authors.initials: L
authors.lastname: Maccioni
authors.forename: Susanna
authors.initials: S
authors.lastname: Barella
authors.forename: Maurizio
authors.initials: M
authors.lastname: Longinotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D017353:Gene Deletion; D005914:Globins / Q000235:genetics*; D006441:Hemoglobin A / Q000032:analysis; D006443:Hemoglobin A2 / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013789:Thalassemia / Q000097:blood / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D005914:Globins; D006441:Hemoglobin A; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin