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

A comprehensive hematological and molecular analysis of 57 β thalassemic heterozygotes, 28 homozygotes, 18 double heterozygotes, 3 compound heterozygotes β thal/β S and one compound heterozygote β thal/Hb Newcastle, in 46 Moroccan families with at least one β thalassemia patient is reported. Six major mutations: β039 (CT), β0FsCD8(−AA), β+IVS1,nt6 (TC) and β0IVS1,nt1 (GA), β0FsCD6 (−A) and β+-29 (AG) cap site account for 75% of the 86 independent β thal chromosomes studied. For the first time, an extensive mutation/haplotype study has been performed on the Moroccan population, and data are consistent with the geographical location of the country and historical links with both the Mediterranean and the Sub-Saharan Africa communities. Despite the heterogeneous spectrum of mutations, good genetic counseling can be offered to the carrier population. This study focuses on the analysis of fetal hemoglobin levels in β thalassemic heterozygotes and its correlation with β globin cluster polymorphic markers in this population. Fetal hemoglobin levels in heterozygotes vary from trace quantities to 17.9% (2.38 g/dl) of total hemoglobin in the adult. No statistically significant correlation was found, either between genders and HbF levels, or between the mutation and the HbF level, with the exception of mutation β0FSCD6(−A). We have examined the α globin genotype and the β globin genotype of heterozygotes, namely, the extended haplotype, which includes the XmnI site at −158 bp of the Gγ gene and the microsatellite (AT)xTy at −540 bp of the β globin gene. In this sample, we confirm the existence of linkage disequilibrium between the CT variation at −158bp of Gγ globin gene (XmnI+) and Orkin's haplotypes III, IV, or IX (the 5′ subhaplotype class A). At 5′ β globin gene, we observe exclusively the allele (AT)7T7. In the β thalassemic heterozygotes studied, no correlation of those genetic markers with HbF levels is observed. Am. J. Hematol. 73:161–168, 2003. © 2003 Wiley-Liss, Inc.