A countrywide prospective study aimed at establishing the prevalence of the haemoglobinopathy genes in the Portuguese population was carried out by screening 15 208 randomly selected blood samples from young males. This male based survey provided the opportunity of assessing simultaneously the prevalence of the red cell enzyme glucose-6-phosphate dehydrogenase (G6PD) deficiency, thus giving a picture of these important hereditary anaemias in Portugal.The results showed a low average frequency of a thalassaemia (0-45%) and haemoglobin S (0-32%) carriers as well as G6PD deficiency (0-51%). However, these disorders are unevenly distributed throughout the country with a higher prevalence in some areas, mainly in the south. The relationship of this pattern of haemoglobinopathies to the known haplotypes linked to fi thalassaemia and sickle cell disease, relevant historical events, and local selective pressure was investigated. Hb D and Hb J are the commonest other structural variants. The implemented programme for control of these hereditary anaemias is described. (J Med Genet 1993;30:235- ResultsThe findings are summarised in the table. Among the 15 208 blood samples analysed for Hb disorders 045% showed I thalassaemia trait (95% confidence limits 045 ± 0011) and 0-32% showed sickle cell trait (95% confidence limits 032 ± 0089). The geographical distribution by administrative districts is shown in figs 1 and 2. The prevalence of both increases from the north (total prevalence less than 0 I %) towards the south (total prevalence more than 2% in three districts).Less common structural variants of haemoglobin were also found, the most frequent being Hb D (n=9) and Hb J (n= 13). Their 235 on 1 September 2018 by guest. Protected by copyright.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. This deficiency in erythrocytes has a prevalence of 0.51 Ϯ 0.109 in the Caucasoid male population of Portugal. The frequency for deficiency-conferring genes is 0.39% in the Portuguese population. In the herein study populations males from areas of Portugal presenting with the highest prevalence of G6PD deficiency (Castelo Branco, Setúbal, Faro, and Lisbon) as well as similar subjects located in the border Center/North area of the country (Viseu) have been analyzed for biochemical parameters and screened for mutations and haplotypeassociated mutations commensurate with G6PD deficiency. Six intragenic restriction fragment length polymorphisms (RFLPs) were studied: exon 5, nt 376 A 3 G, FokI; intron 5, nt 611 C 3 G, PvuII; intron 8, nt 163 C 3 T, BspHI; exon 10, nt 116 G 3 A, PstI; exon 11, nt 1311 C 3 T, BclI; and intron 11, nt 93 T 3 C, NlaIII. New haplotypes were constructed with the inclusion of intron 11, nt 93 T 3 C, NlaIII, and only 5 of 64 possible haplotypes were found to show a marked linkage disequilibrium for several RFLPs and also for mutations and specific haplotypes. The control population (n ϭ 168 males) presented the G6PD B variant and corresponded to haplotypes I (Ϫ Ϫ ϩ ϩ Ϫ Ϫ), Ia (Ϫ Ϫ ϩ ϩ Ϫ ϩ), and VIIa (Ϫ Ϫ ϩ ϩ ϩ ϩ), in 91.8, 2.3, and 5.9%, respectively. The PCR and sequencing analysis of extracted DNAs from the deficient G6PD group showed 48.6% (16/33) of individuals with the G6PD AϪ mutation, corresponding to haplotype VIa (ϩ ϩ Ϫ ϩ Ϫ ϩ); 9% (3/33) with the Betica mutation and 18% (6/33) with the Santa Maria mutation, both of them associated with haplotype IVa (ϩ Ϫ Ϫ ϩ Ϫ ϩ); 6.1% (2/33) with the Mediterranean mutation associated with haplotype VIIa; 12.3% (4/33) with the Seattle mutation, 3.0% (1/33) with Gaohe mutation; and a new mutation, 3.0% (1/33), which we designated by G6PD Flores, all of them associated with haplotype I. © 2002 Elsevier Science (USA)

In Portugal there are a wide variety of G6PD deficiency associated mutations. In an individual from the island of Flores of the Azorean archipelago, we report a new mutation in the G6PD gene that gives rise to a "moderate rate of G6PD deficiency" (12.6% of the normal activity) according to WHO criteria. Direct sequencing revealed a C-->A point mutation at position 1387 with the consequent substitution of an Argine by Serine. We designated this new mutation as G6PD FLORES. The mutation is associated with haplotype I ( - - + + - - ), using six intragenic RFLPs. This information may also be seen as contributing to the clarification of the genetic makeup of the Azorean population, founder mutations, and/or gene flow.