title: Spectrin St Claude, a splicing mutation of the human alpha-spectrin gene associated with severe poikilocytic anemia.
abstract: An alpha-spectrin variant with increased susceptibility to tryptic digestion, alpha(II/47), was previously observed in a child with severe, recessively inherited, poikilocytic anemia. The molecular basis of this variant, spectrin St Claude, has now been identified as a splicing mutation of the alpha-spectrin gene due to a T --> G mutation in the 3' acceptor splice site of exon 20. This polypyrimidine tract mutation creates a new acceptor splice site, AT --> AG, and leads to the production of two novel mRNAs. One mRNA contains a 12 intronic nucleotide insertion upstream of exon 20. This insertion introduces a termination codon into the reading frame and is predicted to encode a truncated protein (108 kD) that lacks the nucleation site and thus cannot be assembled in the membrane. In the other mRNA, there is in-frame skipping of exon 20, predicting a truncated (277 kD) alpha-spectrin chain. The homozygous propositus has only truncated 277 kD alpha-spectrin chains in his erythrocyte membranes. His heterozygous parents are clinically and biochemically normal. This allele was identified in 3% of asymptomatic individuals from Benin, Africa.
authors.affiliation: INSERM U409, Faculté de Médecine Xavier Bichat, Paris, France.
authors.forename: C M
authors.initials: CM
authors.lastname: Fournier
authors.forename: G
authors.initials: G
authors.lastname: Nicolas
authors.forename: P G
authors.initials: PG
authors.lastname: Gallagher
authors.forename: D
authors.initials: D
authors.lastname: Dhermy
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: M C
authors.initials: MC
authors.lastname: Lecomte
mesh_terms: D000328:Adult; D000483:Alleles; D000745:Anemia, Hemolytic, Congenital / Q000097:blood / Q000235:genetics*; D001541:Benin / Q000208:ethnology; D044383:Black People / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004913:Erythrocytes, Abnormal; D005091:Exons / Q000235:genetics; D005602:France; D005787:Gene Frequency; D005838:Genotype; D019430:Guadeloupe / Q000208:ethnology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D016366:Open Reading Frames; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013049:Spectrin / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; C106498:spectrin St. Claude; D013049:Spectrin