title: Thalassaemia-like carriers not linked to the beta-globin gene cluster.
abstract: This study describes the largest series reported to date, of individuals belonging to unrelated families carrying a beta-thalassaemia-like phenotype in whom the beta-globin gene was found to be structurally intact by sequence analysis. This genetic determinant appears haematologically heterogeneous, displaying either a silent beta-thalassaemia-like phenotype or a typical beta-thalassaemia carrier-like phenotype in different families. Compound heterozygosity for both beta-thalassaemia-like determinant and typical beta-thalassaemia allele resulted either in thalassaemia intermedia or thalassaemia major. By linkage analysis both the silent and the typical beta-like determinants were found not to be linked to the beta-globin cluster. Sequence analysis of the hypersensitive site cores of locus control region and of the genes coding for the transcription factors erythroid Kruppel-like factor and nuclear factor (erythroid-derived 2) were normal. beta-globin mRNA levels determined by real-time polymerase chain reaction were reduced in both types of beta-like carriers. These results indicate the existence of causative genetic determinants not yet molecularly defined, but most likely, resulting from either the reduction or loss of function of a gene coding for unknown transcriptional regulator(s) of the beta-globin gene. The knowledge of these rare beta-thalassaemia-like determinants have implications for clinical and, especially, prenatal diagnosis of beta-thalassaemia.
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia, CNR, Cagliari, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Faà
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meloni
authors.forename: Loredana
authors.initials: L
authors.lastname: Moi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ibba
authors.forename: Maurizio
authors.initials: M
authors.lastname: Travi
authors.forename: Antonio
authors.initials: A
authors.lastname: Vitucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rosatelli
mesh_terms: D000483:Alleles; D001803:Blood Transfusion; D002353:Carrier State; D005260:Female; D008040:Genetic Linkage; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007558:Italy; D019901:Locus Control Region; D008297:Male; D005810:Multigene Family; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013789:Thalassemia / Q000235:genetics* / Q000628:therapy
chemical_list: D012333:RNA, Messenger; D005914:Globins