A splice site mutation of alpha-spectrin gene causing skipping of exon 18 in hereditary elliptocytosis.
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.
Alloisio
N
N
CNRS URA 1171, Faculté de Médecine Grange-Blanche, Lyon, France.
Wilmotte
R
R
Maréchal
J
J
Texier
P
P
Denoroy
L
L
Féo
C
C
Benhadji-Zouaoui
Z
Z
Delaunay
J
J
D000483:Alleles; D001483:Base Sequence; D002675:Child, Preschool; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004612:Elliptocytosis, Hereditary / Q000097:blood / Q000235:genetics*; D005091:Exons; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D013049:Spectrin / Q000235:genetics*
D009838:Oligodeoxyribonucleotides; D013049:Spectrin; D004247:DNA