β-spectrinBari: a truncated β-chain responsible for dominant hereditary spherocytosis

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 o...

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Bibliographic Details
Published in:Haematologica (Roma) 2009-12, Vol.94 (12), p.1753-1757
Main Authors: PERROTTA, Silverio, DELLA RAGIONE, Fulvio, LOLASCON, Achille, ROSSI, Francesca, AVVISATI, Rosa Anna, DI PINTO, Daniela, DE MIERI, Giovanna, SCIANGUETTA, Saverio, MANCUSI, Silvia, DE FALCO, Luigia, MARANO, Vito
Format: Article
Language:English
Subjects:
Acanthocytes - pathology
Adult
Anemia, Hemolytic - pathology
Anemias. Hemoglobinopathies
Base Sequence
Biological and medical sciences
Blotting, Western
Brief Reports
Diseases of red blood cells
DNA Mutational Analysis
Family Health
Female
Hematologic and hematopoietic diseases
Humans
Male
Medical sciences
Point Mutation
Reverse Transcriptase Polymerase Chain Reaction
RNA Splice Sites - genetics
Spectrin - genetics
Spectrin - metabolism
Spherocytes - pathology
Spherocytosis, Hereditary - blood
Spherocytosis, Hereditary - genetics
Spherocytosis, Hereditary - pathology
Splenomegaly - pathology
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Summary: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.
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2009.010124