title: Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern Portugal.
abstract: We characterized the genetic nature of beta-thalassaemia in northern Portugal. Of the 164 patients studied three were beta-thalassaemia major cases (one IVS-1-6/beta degrees 39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(-A) mutation was unexpectedly frequent (40%) and associated with the beta-globin haplotype E, and not with the usual European and North African CD6(-A) haplotypes. In contrast, the frequency of IVS-1-6 (8%) and beta degrees 39 (19%) was found to be lower than in the rest of the country. The frequency of all other mutations was similar to previous reports for central/southern Portugal. Six families carried none of the most frequent mutations in the Mediterranean area. These families were studied by gene sequencing, revealing that three families carried a previously described mutation (CD16 G --> A). The remaining families carried previously unidentified mutations: one showed an 86 bp insertion in exon 2 (named HGSA) and two showed a deletion of a cytidine in codon 11 (CD11(-C)). The results, showing a high frequency (82%) of beta degrees mutations, strongly indicates that genetic counselling should be intensified as a means of preventing the spread of the severe mutations found.
authors.affiliation: Clinical Haematology, Santo Antonio General Hospital, Porto; Abel Salazar Institute for the Biomedical Sciences, Porto, Portugal. jcabeda@mail.telepac.pt
authors.forename: J M
authors.initials: JM
authors.lastname: Cabeda
authors.forename: C
authors.initials: C
authors.lastname: Correia
authors.forename: A
authors.initials: A
authors.lastname: Estevinho
authors.forename: C
authors.initials: C
authors.lastname: Simões
authors.forename: M L
authors.initials: ML
authors.lastname: Amorim
authors.forename: L
authors.initials: L
authors.lastname: Pinho
authors.forename: B
authors.initials: B
authors.lastname: Justiça
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D017421:Sequence Analysis; D017086:beta-Thalassemia / Q000453:epidemiology* / Q000235:genetics
chemical_list: D005914:Globins