Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern Portugal

Abstract

Summary.We characterized the genetic nature of bthalassaemia in northern Portugal. Of the 164 patients studied three were b-thalassaemia major cases (one IVS-1-6/ bЊ39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(¹A) mutation was unexpectedly frequent (40%) and associated with the b-globin haplotype E, and not with the usual European and North African CD6(¹A) haplotypes. In contrast, the frequency of IVS-1-6 (8%) and bЊ39 (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(¹C)).The results, showing a high frequency (82%) of bЊ mutations, strongly indicates that genetic counselling should be intensified as a means of preventing the spread of the severe mutations found.

Spectrum of β thalassemia mutations and HbF levels in the heterozygous Moroccan population

“…Confirmation of the ARMS result was performed by restriction enzyme digestion as follows: MboI for ␤ + IVS1,nt110 (G→A) [25], BsabI for ␤ 0 IVS1,nt1 (G→A), MaeI for ␤ 0 39 (C→T), Bsu36I for ␤ 0 FsCD6 (−A), and SfaNI for ␤ + IVS1,nt6 (T→C) [26]. Direct sequencing using ABI Prism 3100 and ABI Prism Big Dye technology from Applied Biosystems was used to detect other mutations.…”

Distribuição das mutações da β-talassemia em Fortaleza, Ceará

“…Há atualmente mais de 200 alelos mutantes descritos (14) . A distribuição e a frequência de mutações das hemoglobinopatias, especialmente para a β-talassemia, já foram caracterizadas na maioria dos países (1,5,13) .…”

Characterization of beta-thalassemia mutations in patients from the state of Rio Grande do Norte, Brazil

“…In Portugal, studies have shown that the most frequently found mutations are β 0 39 (C→T), IVS-I-1 (G→A) and IVS-I-6 (T→C), with frequency varying in accordance with the region (Tamagnini et al , 1983; Cabeda et al , 1999; Faustino et al , 1999). …”