Molecular characterization of an atypical beta-thalassemia caused by a large deletion in the 5' beta-globin gene region.
We describe a Canadian family of Czechoslovakian descent that came to our attention because of an HbA2 percentage approximately twice that of an average case of heterozygous beta-thalassemia. This unique phenotype suggested to us the possibility of a novel genetic mechanism being responsible for their beta-thalassemia. To investigate this possibility, we mapped, cloned, and sequenced the mutant beta-globin allele. This molecular analysis demonstrated the presence of a unique 4,237 base pair (bp) deletion extending from 3.3 kilobases (kb) 5' of the beta-globin mRNA cap site to approximately the middle of beta IVS-2. This truncated beta-globin gene further extends the heterogeneity of mutations known to cause beta-thalassemia and delineates new sequences involved in nonhomologous recombination events in the beta-globin gene region.
D000368:Aged; D001483:Base Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D013789:Thalassemia / Q000235:genetics*
D005914:Globins; D004247:DNA