title: 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.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy. silverio.perrotta@unina2.it
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
authors.forename: Fulvio
authors.initials: F
authors.lastname: Della Ragione
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Rosa Anna
authors.initials: RA
authors.lastname: Avvisati
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Pinto
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Mieri
authors.forename: Saverio
authors.initials: S
authors.lastname: Scianguetta
authors.forename: Silvia
authors.initials: S
authors.lastname: Mancusi
authors.forename: Luigia
authors.initials: L
authors.lastname: De Falco
authors.forename: Vito
authors.initials: V
authors.lastname: Marano
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
mesh_terms: D000050:Acanthocytes / Q000473:pathology; D000328:Adult; D000743:Anemia, Hemolytic / Q000473:pathology; D001483:Base Sequence; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D017354:Point Mutation; D022821:RNA Splice Sites / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013049:Spectrin / Q000235:genetics* / Q000378:metabolism; D013102:Spherocytes / Q000473:pathology; D013103:Spherocytosis, Hereditary / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013163:Splenomegaly / Q000473:pathology
chemical_list: D022821:RNA Splice Sites; D013049:Spectrin