title: Identical G+1 to A mutations in three different introns of the type III procollagen gene (COL3A1) produce different patterns of RNA splicing in three variants of Ehlers-Danlos syndrome. IV. An explanation for exon skipping some mutations and not others.
abstract: Identical G+1 mutations in three different introns of the gene for type III procollagen (COL3A1) that cause aberrant splicing of RNA were found in three probands with life-threatening variants of Ehlers-Danlos syndrome. Because the three mutations were in a gene with multiple and homologous exons, they provided an interesting test for factors that influence aberrant splicing. The G+1 to A mutation in intron 16 caused extensive exon skipping, the G+1 to A mutation in intron 20 caused both use of a cryptic splice site and retention of all the intron sequences, and the G+1 to A mutation in intron 42 caused efficient use of a single cryptic splice site. The different patterns of RNA splicing were not explained by evaluation of potential cryptic splice sites in the introns by either their homology with 5'-splice sites from other genes or by their delta G(0)37 values for binding to U1 RNA. Instead, the results suggested that the patterns of aberrant RNA splicing were primarily determined by the relative rates at which adjacent introns were normally spliced.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: H
authors.initials: H
authors.lastname: Kuivaniemi
authors.forename: S
authors.initials: S
authors.lastname: Kontusaari
authors.forename: G
authors.initials: G
authors.lastname: Tromp
authors.forename: M J
authors.initials: MJ
authors.lastname: Zhao
authors.forename: C
authors.initials: C
authors.lastname: Sabol
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
mesh_terms: D000225:Adenine; D000328:Adult; D002151:Calorimetry; D003001:Cloning, Molecular; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D005091:Exons; D005260:Female; D005796:Genes; D014644:Genetic Variation; D006147:Guanine; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011347:Procollagen / Q000235:genetics*; D015347:RNA Probes; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D013698:Templates, Genetic
chemical_list: D011347:Procollagen; D015347:RNA Probes; D012342:RNA, Small Nuclear; D006147:Guanine; D000225:Adenine