First description of a frameshift mutation in the α1-globin gene associated with α1-thalassaemia

Abstract

A frameshift mutation in the α1-globin gene, responsible for a clinically mild α1-thalassaemia phenotype, has been characterized in a Spanish woman. After excluding the most common forms of α1-thalassaemia found in the Mediterranean area, both α1-globin genes (α1 and α2) were amplified and analysed selectively by non-radioactive single-strand conformation polymorphism (SSCP). An abnormal SSCP mobility was present in the second exon of the α1-globin gene and direct sequence analysis revealed a 13 bp deletion (between codons 51 and 55) affecting a single allele. The consequence of this mutation is a reading frameshift leading to a novel amino acid coding sequence from codons 51-61 and a premature stop signal at new position 62, which results in a net reduction of the affected α1-globin chain output. The presence of this new mutation was confirmed by restriction enzyme analysis of the specific PCR product.