The beta-thalassemia mutation/haplotype distribution in the moroccan population

The present study compiles the results of our own research and of a prior study on beta-thalassemia (thal) in Morocco, comprising a total of 187 beta-thalassemic chromosomes. Six major mutations: (beta0) codon 39 (C --> T), (beta+) IVS-I-6 (T --> C), (beta0) frameshift codon (FSC) 6 (-A), (beta0) FSC 8 (-AA), (beta0) IVS-I-1 (G --> A) and (beta+) -29 (A --> G) account for 75.7% of the independent chromosomes studied. A regional predominance was observed (Gharb and West regions) for the (beta+) IVS-I-6 (T --> C) mutation. Despite an observed heterogeneity of molecular anomalies, a direct method of diagnosis of the prevalent mutations is feasible in this population. The distributions of mutations and haplotypes are in conformity with the geographical location of Morocco and the historical links with both the Mediterranean communities that have successively interspersed with the Berbers, the Phoenicians, the Carthaginians, the Romans, the Arabs, the population of the Iberian Peninsula and, to a lesser degree, the Vandals and the Byzantines and permanently, with the Sub-Saharan Africans. In the adult population, the levels of fetal hemoglobin (Hb) in heterozygotes vary from trace quantities to 2.38 g/dL of total Hb. With the exception of the (beta0) codon 39 (C --> T) nonsense mutation, no statistically significant correlation was found, neither between mutation and Hb F levels, nor gender and Hb F levels in heterozygotes. The genetic markers for Hb F increase, located within cis active sites such as the XmnI site at -158 bp of the Ggamma-globin gene and the AT(X)T(Y) repeat region at -540 bp of the beta-globin gene, were assessed. The polymorphism XmnI shows linkage disequilibrium with haplotypes III, IV and IX, as previously observed in the Algerian, Sicilian and Portuguese beta-thal populations. Contrary to what has previously been reported for a population of beta-thal carriers of European descent, this sample does not show a statistically significant correlation between Hb F levels and the presence of the genetic markers XmnI restriction site at -158 bp of the Ggamma-globin gene and AT(X)T(Y) alleles at 5' of the beta-globin gene.