title: A splice site mutation of the beta-spectrin gene causing exon skipping in hereditary elliptocytosis associated with a truncated beta-spectrin chain.
abstract: We studied a French kindred with hereditary elliptocytosis associated with a spectrin variant (spectrin LePuy) containing a beta-spectrin chain that is truncated at its C terminus (Dhermy, D., Lecomte, M., Garbarz, M., Bournier, O., Galand, C., Gautero, H., Feo, C., Alloisio, N., Delaunay, J., and Boivin, P. (1982) J. Clin. Invest. 70, 707-715). The structure of the 3' end of the beta-spectrin gene, the region encoding the C terminus of beta-spectrin, was determined. Nucleotide sequencing of amplified genomic DNA revealed a mutation at position +4 (A----G) of the 5' donor consensus splice site of the intron following the third-to-last exon (exon X) in one beta-spectrin allele of a heterozygous patient. Agarose gel electrophoresis of polymerase chain reaction-amplified cDNA revealed an extra band of lower molecular weight, suggesting that the shortened beta-spectrin chain of spectrin LePuy arises from aberrant mRNA splicing. Nucleotide sequencing of the shorter cDNA amplification product revealed that the sequences encoding exon X were absent. Southern blotting of cDNA amplification products confirmed this result. The skipping of exon X causes a shift in the normal reading frame resulting in the encoding of a new amino acid sequence at the C terminus of the mutant beta-spectrin chain. A new in-frame stop codon is encountered following a single residue of this novel sequence.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: P G
authors.initials: PG
authors.lastname: Gallagher
authors.forename: W T
authors.initials: WT
authors.lastname: Tse
authors.forename: F
authors.initials: F
authors.lastname: Costa
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
authors.forename: P
authors.initials: P
authors.lastname: Boivin
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
authors.forename: B G
authors.initials: BG
authors.lastname: Forget
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D004612:Elliptocytosis, Hereditary / Q000235:genetics*; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D013049:Spectrin / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D013049:Spectrin; D004247:DNA