{beta}-spectrinBari: a truncated {beta}-chain responsible for dominant hereditary spherocytosis.

We describe a b-spectrin variant, named b-spectrin Bari, characterized by a truncated chain and associated with hereditary spherocytosis. The clinical phenotype consists of a moderately severe hemolytic anemia, splenomegaly, and spherocytes and acanthocytes in the blood smear. The occurrence of the truncated protein, that represents about 8% of the total b-spectrin occurring on the membrane, results in a marked spectrin deficiency. The altered protein is due to a single point mutation at position –2 (A->G) of the acceptor splice site of intron 16 leading to an aberrant b-spectrin message skipping exons 16 and 17 indistinguishable from that reported for b-spectrin Winston-Salem. We provide evidence that the mutated gene is transcribed but its mRNA is less abundant than either its normal counterpart or b-spectrin Winston-Salem mRNA. Our findings are an example of how mutations in different splice sites, although causing the same truncating effect, result in clearly different clinical pictures.