Spectrin Cosenza: a novel Beta chain variant associated with Sp AlphaI/74 hereditary elliptocytosis

A Calabrian family (Southern Italy) with Sp (alpha(I/74) hereditary elliptocytosis (HE) in the heterozygous state was studied. Sp alpha(I/74) HE is associated with asymptomatic elliptocytosis, a defect in spectrin dimer self association and an increase of the alpha(I/74) kD fragment from the cr chain after partial tryptic digestion of spectrin. To identify the underlying molecular defect, we analysed exons V, W, X, Y, Z of the beta gene and exon 2 of the alpha gene by single-strand conformational polymorphism (SSCP) of the amplification products. Direct DNA sequencing of the mutant exon showed a C --> G substitution at position 6284 of the beta gene. The corresponding substitution at the protein level was Arg --> Pro in the 2064 position of the beta-spectrin chain.