Published online 16 July 2009
Haematologica, Vol 94, Issue 12, 1753-1757 doi:10.3324/haematol.2009.010124
Copyright © 2009 by Ferrata Storti Foundation

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Perrotta, S. Articles by Iolascon, A. PubMed PubMed Citation Articles by Perrotta, S. Articles by Iolascon, A.

Red Cell Disorders

β-spectrin^Bari: a truncated β-chain responsible for dominant hereditary spherocytosis

Silverio Perrotta¹, Fulvio Della Ragione², Francesca Rossi¹, Rosa Anna Avvisati³, Daniela Di Pinto¹, Giovanna De Mieri¹, Saverio Scianguetta¹, Silvia Mancusi¹, Luigia De Falco³, Vito Marano¹, Achille Iolascon³

¹ Department of Pediatrics, Second University of Naples, Naples
² Department of Biochemistry and Biophysics "F. Cedrangolo", Second University of Naples, Naples
³ Medical Genetics, Department of Biochemistry and Medical Biotechnologies, University Federico II of Naples, CEINGE-Advanced Biotechnologies, Naples, Italy

Correspondence: Silverio Perrotta, MD, Department of Pediatrics, Second University of Naples, Via Luigi De Crecchio, 4 Naples, Italy. E-mail: silverio.perrotta{at}unina2.it

We describe a β-spectrin variant, named β-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 β-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 β-spectrin message skipping exons 16 and 17 indistinguishable from that reported for β-spectrin Winston-Salem. We provide evidence that the mutated gene is transcribed but its mRNA is less abundant than either its normal counterpart or β-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.

Key words: β-spectrin, truncated β-chain, hereditary spherocytosis.