Perrotta S, Della Ragione F, Rossi F, Avvisati RA, Di Pinto D, De Mieri G, Scianguetta S, Mancusi S, De Falco L, Marano V, Iolascon A
{beta}-spectrinBari: a truncated {beta}-chain responsible for dominant hereditary spherocytosis. [JOURNAL ARTICLE]
Haematologica 2009 Jul 16.
We describe a beta-spectrin variant, named beta-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 the reported for beta-spectrin Winston-Salem. We provide evidence that the mutated gene is transcribed but its mRNA is less abundant than either its normal counterpart or beta-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.
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