A splice site mutation of the β-spectrin gene causing exon skipping in hereditary elliptocytosis associated with a truncated β-spectrin chain

Patrick G. Gallagher, William T. Tse, Fernando Costa, Alphonse Scarpa, Pierre Boivin, Jean Delaunay, Bernard G. Forget

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Abstract

We studied a French kindred with hereditary elliptocytosis associated with a spectrin variant (spectrin LePuy) containing a β-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 β-spectrin gene, the region encoding the C terminus of β-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 β-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 β-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 β-spectrin chain. A new in-frame stop codon is encountered following a single residue of this novel sequence.

Original languageEnglish (US)
Pages (from-to)15154-15159
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number23
StatePublished - Oct 2 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Gallagher, P. G., Tse, W. T., Costa, F., Scarpa, A., Boivin, P., Delaunay, J., & Forget, B. G. (1991). A splice site mutation of the β-spectrin gene causing exon skipping in hereditary elliptocytosis associated with a truncated β-spectrin chain. Journal of Biological Chemistry, 266(23), 15154-15159.