title: A mutation in the pro alpha 2(I) gene (COL1A2) for type I procollagen in Ehlers-Danlos syndrome type VII: evidence suggesting that skipping of exon 6 in RNA splicing may be a common cause of the phenotype.
abstract: Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal amounts of normal and shortened pro alpha 2(I) chains of type I procollagen. Nuclease S1 probe protection experiments with mRNA demonstrated that the pro alpha 2(I) chains were shortened because of a deletion of most or all of the 54 nucleotides in exon 6, the exon that contains codons for the cleavage site for procollagen N-proteinase. Sequencing of genomic clones revealed a single-base mutation that converted the first nucleotide of intron 6 from G to A. Therefore, the mutation was a change, in the -GT-consensus splice site, that produced efficient exon skipping. Allele-specific oligonucleotide hybridizations demonstrated that the proband's mother, father, and brother did not have the mutation. Therefore, the mutation was a sporadic one. Analysis of potential 5' splice sites in the 5' end of intron 6 indicated that none had favorable values by the two commonly employed techniques for evaluating such sites. The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene. No other mutations in the two type I procollagen genes have been found in the syndrome. Therefore, such mutations may be a common cause of the phenotype. The primers developed should be useful in screening for the same or similar mutations causing the disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-6799.
authors.forename: N S
authors.initials: NS
authors.lastname: Vasan
authors.forename: H
authors.initials: H
authors.lastname: Kuivaniemi
authors.forename: B E
authors.initials: BE
authors.lastname: Vogel
authors.forename: R R
authors.initials: RR
authors.lastname: Minor
authors.forename: J A
authors.initials: JA
authors.lastname: Wootton
authors.forename: G
authors.initials: G
authors.lastname: Tromp
authors.forename: R
authors.initials: R
authors.lastname: Weksberg
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D004586:Electrophoresis; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D011347:Procollagen; D012333:RNA, Messenger; D004247:DNA