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

Abstract

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 beta-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 beta-spectrin message skipping exons 16 and 17 indistinguishable from that 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.

• Authors: 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
• Journal: Haematologica (Haematologica) Vol. 94 Issue 12 Pg. 1753-7 (Dec 2009) ISSN: 1592-8721 [Electronic] Italy
• PMID: 19608679 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA Splice Sites
• Spectrin

Topics

• Acanthocytes (pathology)
• Adult
• Anemia, Hemolytic (pathology)
• Base Sequence
• Blotting, Western
• DNA Mutational Analysis
• Family Health
• Female
• Humans
• Male
• Point Mutation
• RNA Splice Sites (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Spectrin (genetics, metabolism)
• Spherocytes (pathology)
• Spherocytosis, Hereditary (blood, genetics, pathology)
• Splenomegaly (pathology)