ANKYRIN-NAPOLI - A DE-NOVO DELETIONAL FRAMESHIFT MUTATION IN EXON-16 OF ANKYRIN GENE (ANK1) ASSOCIATED WITH SPHEROCYTOSIS

We report case of apparently recessive hereditary spherocytosis in an Italian child. The proband exhibited a reduction of overall ankyrin in the red cell membrane. The parents were free of any haematological ma nifestations. The VNDR associated with the ankyrin gene (ANK1) were co nsistent with the following diplotypes: AC(11)/AC(14) (father), AC(14) /AC(14) (mother) and AC(11)/AC(14) (child). The cDNA of the patient di sclosed the expression ofthe AC(11) allele only. As a consequence, we put forward the hypothesis of a de novo inactivation affecting the ank yrin allele of maternal origin (AC(14)) and accounting for the disease . PCR amplification of exons, SSCP analysis and nucleotide sequencing disclosed a polymorphism: GAC --> AAC; Asp --> Asn in codon 328 of exo n 10, and a one-nucleotide deletion : CTG --> CG in codon 573 of the e xon 16. This frameshift mutation placed in phase the TGA triplet that normally overlaps codons 636 and 637. Termination of translation near the middle of ankyrin mRNA coding sequence resulted. presumably, in it s premature degradation. The present allele has been designated allele Napoli.