title: Novel promoter and splice junction defects add to the genetic, clinical or geographic heterogeneity of beta-thalassaemia in the Portuguese population.
abstract: In order to delineate the spectrum and the relative abundance of beta-globin gene defects causing thalassaemia in the Portuguese population, a representative sample was analysed including 51 beta-thalassaemia carriers along with 26 patients representing different clinical phenotypes. Seven mutations were identified, four of which [codon 39 (C----T), 39%; intervening sequence (IVS) 1 nucleotide (nt) 1 (G----A), 26%; IVS 1 nt 110 (G----A), 17%; IVS 1 nt 6 (T----C), 15%] account for 97% of 93 beta-thalassaemia chromosomes. Two previously undescribed mutations, namely a C----T substitution at position--90 in the proximal CACCC box, and the deletion of nucleotides 4 and 5 (AG) in IVS2 were identified. The uncommon, though ubiquitous, G----T transversion at codon 121 was found once upon haplotype V. Direct prenatal diagnosis can be offered to 95% of couples at risk of bearing a thalassaemic child.
authors.affiliation: Laboratório de Genética Humana, Instituto Nacional de Saúde, Lisboa, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Faustino
authors.forename: L
authors.initials: L
authors.lastname: Osório-Almeida
authors.forename: J
authors.initials: J
authors.lastname: Barbot
authors.forename: D
authors.initials: D
authors.lastname: Espírito-Santo
authors.forename: J
authors.initials: J
authors.lastname: Gonçalves
authors.forename: L
authors.initials: L
authors.lastname: Romão
authors.forename: M C
authors.initials: MC
authors.lastname: Martins
authors.forename: M M
authors.initials: MM
authors.lastname: Marques
authors.forename: J
authors.initials: J
authors.lastname: Lavinha
mesh_terms: D002869:Chromosome Aberrations / Q000235:genetics*; D007446:Chromosome Inversion; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005914:Globins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation; D011174:Portugal / Q000453:epidemiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012326:RNA Splicing; D013789:Thalassemia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D003062:Codon; D005914:Globins