title: A 5' splice region G-->C mutation in exon 3 of the human beta-spectrin gene leads to decreased levels of beta-spectrin mRNA and is responsible for dominant hereditary spherocytosis (spectrin Guemene-Penfao).
abstract: We studied a family with autosomal dominant hereditary spherocytosis (HS) associated with a mild spectrin deficiency. Linkage analysis using two microsatellite markers (D14S63 and D14S271) very close to the beta-spectrin gene (SPTB) showed that HS co-segregated with alleles of these microsatellite markers and the linkage between the marker and HS was statistically significant. The presence of a beta-spectrin protein polymorphism (beta-spectrin Vay; A1880V) in trans of the HS allele was not itself deleterious, but allowed the detection of decreased membrane expression of the spherocytic beta-spectrin allele in two HS-affected subjects. Direct sequencing of the coding exons of the beta-spectrin gene in one affected subject showed the presence of a G-->C transversion at the terminal nucleotide of exon 3, which did not change the leucine codon 100 (CTG-->CTC). The presence of the mutation was confirmed by restriction enzyme digestion at the DNA level in all affected SH members of the family. The G-->C mutation severely reduced the utilization of the 5' splice site and resulted in aberrant mRNA splicing with intron 3 retention.
authors.affiliation: INSERM U409, Association Claude Bernard, Faculté de Médecine Xavier Bichat, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Garbarz
authors.forename: C
authors.initials: C
authors.lastname: Galand
authors.forename: D
authors.initials: D
authors.lastname: Bibas
authors.forename: O
authors.initials: O
authors.lastname: Bournier
authors.forename: I
authors.initials: I
authors.lastname: Devaux
authors.forename: J L
authors.initials: JL
authors.lastname: Harousseau
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: D
authors.initials: D
authors.lastname: Dhermy
mesh_terms: D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013049:Spectrin / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D013049:Spectrin