β-spectrinBari: a truncated β-chain responsible for dominant hereditary spherocytosis
Silverio Perrotta, Fulvio Della Ragione, Francesca Rossi, Rosa Anna Avvisati, Daniela Di Pinto, Giovanna De Mieri, Saverio Scianguetta, Silvia Mancusi, Luigia De Falco, Vito Marano, Achille Iolascon

Author Affiliations

  1. Silverio Perrotta1,
  2. Fulvio Della Ragione2,
  3. Francesca Rossi1,
  4. Rosa Anna Avvisati3,
  5. Daniela Di Pinto1,
  6. Giovanna De Mieri1,
  7. Saverio Scianguetta1,
  8. Silvia Mancusi1,
  9. Luigia De Falco3,
  10. Vito Marano1 and
  11. Achille Iolascon3
  1. 1 Department of Pediatrics, Second University of Naples, Naples, Italy
  2. 2 Department of Biochemistry and Biophysics “F. Cedrangolo”, Second University of Naples, Naples, Italy
  3. 3 Medical Genetics, Department of Biochemistry and Medical Biotechnologies, University Federico II of Naples, CEINGE-Advanced Biotechnologies, Naples, Italy
  1. 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

Abstract

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 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 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.

  • Received April 14, 2009.
  • Revision received June 12, 2009.
  • Accepted June 16, 2009.