Spectrin Cosenza: a novel β chain variant associated with Sp αI/74 hereditary elliptocytosis

A Calabrian family (Southern Italy with Sp α I/74 hereditary elliptocytosis (HE) in the heterozygous state was studied. Sp α I/74 HE is associated with asymptomatic elliptocytosis, a defect in spectrin dimer self association and an increase of the α I/74 kD fragment from the a chain after partial tryptic digestion of spectrin. To identify the underlying molecular defect, we analysed exons V W, X, Y, Z of the β gene and exon 2 of the α 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 β gene. The corresponding substitution at the protein level was Arg → Pro in the 2064 position of the β-spectrin chain.