SPECTRIN COSENZA - A NOVEL BETA-CHAIN VARIANT ASSOCIATED WITH SP ALPHA(I 74) HEREDITARY ELLIPTOCYTOSIS/

A Calabrian family (Southern Italy) with Sp (alpha(I/74) hereditary el liptocytosis (HE) in the heterozygous state was studied. Sp alpha(I/74 ) HE is associated with asymptomatic elliptocytosis, a defect in spect rin dimer self association and an increase of the alpha(I/74) kD fragm ent 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 con formational polymorphism (SSCP) of the amplification products. Direct DNA sequencing of the mutant exon showed a C --> G substitution at pos ition 6284 of the beta gene. The corresponding substitution at the pro tein level was Arg --> Pro in the 2064 position of the beta-spectrin c hain.