title: Spectrin Tunis (Sp alpha I/78), an elliptocytogenic variant, is due to the CGG----TGG codon change (Arg----Trp) at position 35 of the alpha I domain.
abstract: Spectrin Tunis (Sp alpha I/78) is an alpha l domain variant that causes asymptomatic elliptocytosis in the heterozygote state. It is manifested by a reduction of spectrin dimer self-association and by the development of a major 78-Kd fragment at the expense of the alpha l 80-Kd fragment upon spectrin-limited digestion. Amino acid sequence analysis, following peptide transfer onto Immobilon membranes, showed that the 78-Kd fragment results from a sensitized cleavage after lysyl residue 10. Using a 13.5-kb genomic alpha-spectrin probe and the Xbal, Pvull, and Mspl polymorphic sites detected with this probe, we concluded that spectrin Tunis is associated with the + - + haplotype (in the above order). Twenty mer oligonucleotides, complementary to genomic segments from introns 2 and 3, respectively, were synthesized. We then performed DNA amplification and sequencing. In the two investigated carriers of spectrin Tunis, we found the C----T base substitution of the codon corresponding to position 35 of the alpha l domain (CGG----TGG; Arg----Trp). The mutation lies in the last part of an alpha helix that extends from residues 9 to 44 of partial repeat alpha 1' and is comparable with helix 3 of full repeats 1 to 5. The modified proteolytic site, located 25 amino acid residues upstream, occurs at the beginning of the helix.
authors.affiliation: CNRS URA 1171, Faculté de Médecine Grange-Blanche, Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Morlé
authors.forename: F
authors.initials: F
authors.lastname: Morlé
authors.forename: A F
authors.initials: AF
authors.lastname: Roux
authors.forename: J
authors.initials: J
authors.lastname: Godet
authors.forename: B G
authors.initials: BG
authors.lastname: Forget
authors.forename: L
authors.initials: L
authors.lastname: Denoroy
authors.forename: M
authors.initials: M
authors.lastname: Garbarz
authors.forename: D
authors.initials: D
authors.lastname: Dhermy
authors.forename: R
authors.initials: R
authors.lastname: Kastally
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D004612:Elliptocytosis, Hereditary / Q000097:blood / Q000235:genetics*; D005784:Gene Amplification; D014644:Genetic Variation; D006239:Haplotypes; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000302:isolation & purification; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000235:genetics*; D013049:Spectrin / Q000235:genetics* / Q000302:isolation & purification; D014364:Tryptophan / Q000235:genetics
chemical_list: D003062:Codon; D010446:Peptide Fragments; D012333:RNA, Messenger; C060463:spectrin Tunis; D013049:Spectrin; D014364:Tryptophan; D001120:Arginine