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A splice site mutation of alpha-spectrin gene causing skipping of exon 18
in hereditary elliptocytosis
N Alloisio, R Wilmotte, J Marechal, P Texier, L Denoroy, C Feo, Z Benhadji- Zouaoui and J Delaunay
CNRS URA 1171, Faculte de Medecine Grange-Blanche, Lyon, France.
Spectrin Oran (alpha II/21) has been reported previously as a variant of
the alpha II domain. Its expression level is low (10% of total spectrin) in
heterozygotes denoting a major disadvantage of the mutated alpha-chain
dimer or tetramer with respect to their normal counterparts. Spectrin Oran
is associated with symptomatic elliptocytosis in the homozygous state. A
1-minute digestion time allowed to perceive a fast trypsin cleavage (not
existing normally) after Arg 890 (helix 3 of repeating segment alpha 9).
The responsible change was the lack of amino acids 822 to 862 (helix 2 of
repeating segment alpha 8). Such a situation fits with the phasing of
spectrin according to which mutated helix 2 and distorted helix 3 are
adjacent to one another. The internal position of the structural change
accounts for the slight self-association defect. The ultimate genetic
lesion was a G to A substitution (intronic position-1) in the acceptor
splice site of intron 17 resulting in skipping of exon 18. The substitution
also created an acceptor splice site 1 base downstream, but the latter was
used at a low grade.
Volume 81,
Issue 10,
pp. 2791-2798,
05/15/1993
Copyright © 1993 by The American Society of Hematology
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