title: Spectrum of beta thalassemia mutations and HbF levels in the heterozygous Moroccan population.
abstract: A comprehensive hematological and molecular analysis of 57 beta thalassemic heterozygotes, 28 homozygotes, 18 double heterozygotes, 3 compound heterozygotes beta thal/beta S and one compound heterozygote beta thal/Hb Newcastle, in 46 Moroccan families with at least one beta thalassemia patient is reported. Six major mutations: beta(0)39 (C-->T), beta(0)FsCD8(-AA), beta(+)IVS1,nt6 (T-->C) and beta(0)IVS1,nt1 (G-->A), beta(0)FsCD6 (-A) and beta(+)-29 (A-->G) cap site account for 75% of the 86 independent beta 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 beta thalassemic heterozygotes and its correlation with beta 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 beta(0)FSCD6(-A). We have examined the alpha globin genotype and the beta globin genotype of heterozygotes, namely, the extended haplotype, which includes the XmnI site at -158 bp of the Ggamma gene and the microsatellite (AT)(x)T(y) at -540 bp of the beta globin gene. In this sample, we confirm the existence of linkage disequilibrium between the C-->T variation at -158 bp of Ggamma globin gene (XmnI(+)) and Orkin's haplotypes III, IV, or IX (the 5' subhaplotype class A). At 5' beta globin gene, we observe exclusively the allele (AT)(7)T(7). In the beta thalassemic heterozygotes studied, no correlation of those genetic markers with HbF levels is observed.
authors.affiliation: Laboratório de Genética Molecular, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Lemsaddek
authors.forename: Isabel
authors.initials: I
authors.lastname: Picanço
authors.forename: Filomena
authors.initials: F
authors.lastname: Seuanes
authors.forename: Lahoucine
authors.initials: L
authors.lastname: Mahmal
authors.forename: Saâd
authors.initials: S
authors.lastname: Benchekroun
authors.forename: Mohammed
authors.initials: M
authors.lastname: Khattab
authors.forename: Paulo
authors.initials: P
authors.lastname: Nogueira
authors.forename: Leonor
authors.initials: L
authors.lastname: Osório-Almeida
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D005914:Globins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009018:Morocco; D020125:Mutation, Missense; D017384:Sequence Deletion; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005914:Globins; D004247:DNA; D005319:Fetal Hemoglobin