High incidence of the CD8/9 (+G) beta(0)-thalassemia mutation in Spain

Background and Objective. In Spain, as in other Mediterranean regions the m ost common beta-thalassemia mutations are due to point mutations in gene re gions that are critical for production of mRNA, such as [IVS-I-nt1 (G-->A), IVS-I-nt6 (T-->C), IVS-I-nt110 (G-->A)] which interrupt normal RNA process ing or nonsense mutations [CD39 (C-->T)] which interrupt the translation of mRNA. The frameshift mutation CD8/9 (+G) is a very common allele in Asian Indians but is rare in the Mediterranean regions in which isolated alleles with this mutation have been found in Israel, Greece, Portugal and Turkey. Design and Methods. We performed a molecular analysis of 175 chromosomes co rresponding to 233 beta-thalassemia patients (221 heterozygous, 10 homozygo us and 2 compound heterozygous) who belong to 169 Spanish families. The stu dy of beta-thalassemia was made by PCR-ARMS, the alpha genes by Southern bl ot, the phenotype of Hb Lepore by enzymatic amplification and the presence of -158 gamma(G) C-->T mutation by PCR and digestion with the restriction e nzyme XmnL. Results. Twenty of these 233 patients showed the beta-thalassemia mutation CD8/9 (+G) (17 were heterozygous, 2 homozygous and in one patient the mutat ion was associated with a structural variant Hb Leg ore Boston). Interpretation and Conclusions. These data reveal the heterogeneity of beta -thalassemia in Spain and the relatively high frequency (8.6%) of the frame shift mutation CD8/9 (+G). It is surprising that homozygotes for beta(o)-th alassemia due to this mutation with very high Hb F values (around 90%) pres ent a phenotype of intermediate thalassemia. (C) 1998, Ferrata Storti Found ation.