title: A stop codon mutation in COL11A2 induces exon skipping and leads to non-ocular Stickler syndrome.
abstract: Mutations in COL11A2 cause a spectrum of phenotypes affecting chondrogenic tissues. We analyzed this gene by conformation sensitive gel electrophoresis (CSGE) and sequencing in a family with non-ocular Stickler syndrome, and found a heterozygous C --> T mutation in exon 57 + 13 in affected members, resulting in Arg893Stop codon. Since heterozygous nonsense mutations in COL11A2 do not usually lead to any obvious phenotype, all exons and exon boundaries of COL11A2 in the sample of the propositus were sequenced. Because no disease-associated alterations were found, we performed RT-PCR analysis on the RNA. Analysis showed skipping of exon 57 in one allele, resulting in an inframe deletion of 54 bp or 18 amino acids, which would explain the phenotype observed in the family. Thus, the exon skipping resulted from a nonsense-associated altered splicing (NAS). This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.
authors.affiliation: Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland.
authors.forename: Mirka Marjanna
authors.initials: MM
authors.lastname: Vuoristo
authors.forename: John Georgios
authors.initials: JG
authors.lastname: Pappas
authors.forename: Valerie
authors.initials: V
authors.lastname: Jansen
authors.forename: Leena
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D024161:Collagen Type XI / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005192:Family Health; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000473:pathology; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011506:Proteins / Q000235:genetics; D013577:Syndrome
chemical_list: C499319:COL11A2 protein, human; D018389:Codon, Nonsense; D024161:Collagen Type XI; D011506:Proteins