Abstract
The silent carrier of β thalassemia has a decreased β/α globin synthesis ratio, but normal Hb A2 and Hb F levels and red cell indices. We have restudied the first described family (N. Engl. J. Med. 281:1327, 1969), in which the father is a silent carrier,the mother has high Hb A2 β-thalassemia trait, and both children have β thalassemia of intermediate clinical severity. The relative excess α globin in this family is not due to an increase in α-globin gene numbers. The maternal and paternal β-globin genes were cloned from the daughter's genomic DNA. The maternal gene contains a previously reported IVS-1 splice junction βo thalassemia mutation. Sequence analysis of the paternal gene failed to reveal any base changes of functional significance. In HeLa cells the gene was expressed at normal levels with proper processing of RNA. Haplotype analysis revealed that the affected son and daughter inherited different εγδβ-globin gene clusters from the father. However, the father was homozygous for all polymorphic restriction sites downstream from a Taq I site approximately 3 kb 5' to the δ-globin gene. Two explanations for these results are: (1) recombination within primordial germ cells of the father occurred downstream from the Taq I site (2) the paternal silent carrier allele is not linked to the β-globin cluster. Studies which distinguish between these possibilities are in progress. In either case, the mutation responsible for β thalassemia is outside the region analyzed by structural and functional studies.
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Semenza, G., Delgrosso, K., Surrey, S. et al. THE SILENT CARRIER ALLELE: β-THALASSEMIA WITHOUT A MUTATION IN THE β-GLOBIN GENE REGION. Pediatr Res 18 (Suppl 4), 248 (1984). https://doi.org/10.1203/00006450-198404001-00931
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DOI: https://doi.org/10.1203/00006450-198404001-00931