PURPOSE: To determine the molecular defect in a family with autosomal dominant rhegmatogenous retinal detachment (DRRD), and to investigate missplicing as a possible phenotypic modifier of mutations in COL2A1. METHODS: Clinical examination of the family and linkage analysis using markers flanking COL2A1 and COL11A1, the known loci for Stickler syndrome; mutation screening of COL2A1; construction of splicing reporter minigenes and transfection into cultured cells; and RT-PCR analysis of reporter specific transcripts. RESULTS: A family with DRRD showed no systemic clinical signs (skeletal, orofacial, or auditory) usually associated with Stickler syndrome. Linkage analysis excluded COL11A1 as the disease locus but could not exclude COL2A1. Mutation screening of COL2A1 identified a novel G118R mutation in type II collagen. Transfection of minigenes carrying mutations associated with DRRD (G118R, R453X, and L467F) into cultured cells detected no missplicing of mRNA from mutant constructs. CONCLUSIONS: Mutations outside the alternatively spliced exon 2 region of COL2A1 can also result in an ocular only phenotype. There was no evidence that missplicing modifies the phenotype of these mutations, suggesting that the minimal or absent systemic features demonstrated by the G118R and L467F mutations are the result of the biophysical changes imparted on the collagen molecule.
PURPOSE: To determine the molecular defect in a family with autosomal dominant rhegmatogenous retinal detachment (DRRD), and to investigate missplicing as a possible phenotypic modifier of mutations in COL2A1. METHODS: Clinical examination of the family and linkage analysis using markers flanking COL2A1 and COL11A1, the known loci for Stickler syndrome; mutation screening of COL2A1; construction of splicing reporter minigenes and transfection into cultured cells; and RT-PCR analysis of reporter specific transcripts. RESULTS: A family with DRRD showed no systemic clinical signs (skeletal, orofacial, or auditory) usually associated with Stickler syndrome. Linkage analysis excluded COL11A1 as the disease locus but could not exclude COL2A1. Mutation screening of COL2A1 identified a novel G118R mutation in type II collagen. Transfection of minigenes carrying mutations associated with DRRD (G118R, R453X, and L467F) into cultured cells detected no missplicing of mRNA from mutant constructs. CONCLUSIONS: Mutations outside the alternatively spliced exon 2 region of COL2A1 can also result in an ocular only phenotype. There was no evidence that missplicing modifies the phenotype of these mutations, suggesting that the minimal or absent systemic features demonstrated by the G118R and L467F mutations are the result of the biophysical changes imparted on the collagen molecule.
Authors: Zack Soh; Allan J Richards; Annie McNinch; Philip Alexander; Howard Martin; Martin P Snead Journal: Genes (Basel) Date: 2022-06-18 Impact factor: 4.141
Authors: Thibaud S Boutin; David G Charteris; Aman Chandra; Susan Campbell; Caroline Hayward; Archie Campbell; Priyanka Nandakumar; David Hinds; Danny Mitry; Veronique Vitart Journal: Hum Mol Genet Date: 2020-03-13 Impact factor: 6.150
Authors: Sarra E Jamieson; Lee-Anne de Roubaix; Mario Cortina-Borja; Hooi Kuan Tan; Ernest J Mui; Heather J Cordell; Michael J Kirisits; E Nancy Miller; Christopher S Peacock; Aubrey C Hargrave; Jessica J Coyne; Kenneth Boyer; Marie-Hélène Bessieres; Wilma Buffolano; Nicole Ferret; Jacqueline Franck; François Kieffer; Paul Meier; Dorota E Nowakowska; Malgorzata Paul; François Peyron; Babill Stray-Pedersen; Andrea-Romana Prusa; Philippe Thulliez; Martine Wallon; Eskild Petersen; Rima McLeod; Ruth E Gilbert; Jenefer M Blackwell Journal: PLoS One Date: 2008-06-04 Impact factor: 3.240
Authors: Frederic R E Acke; Ingeborg J M Dhooge; Fransiska Malfait; Els M R De Leenheer Journal: Orphanet J Rare Dis Date: 2012-10-30 Impact factor: 4.123