Beta-spectrinBari: a truncated beta-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 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.
Perrotta
Silverio
S
Department of Pediatrics, Second University of Naples, Naples, Italy. silverio.perrotta@unina2.it
Della Ragione
Fulvio
F
Rossi
Francesca
F
Avvisati
Rosa Anna
RA
Di Pinto
Daniela
D
De Mieri
Giovanna
G
Scianguetta
Saverio
S
Mancusi
Silvia
S
De Falco
Luigia
L
Marano
Vito
V
Iolascon
Achille
A
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
D022821:RNA Splice Sites; D013049:Spectrin