Document Detail

A novel mutation of COL2A1 resulting in dominantly inherited rhegmatogenous retinal detachment.
MedLine Citation:
PMID:  15671297     Owner:  NLM     Status:  MEDLINE    
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.
Allan J Richards; Sarah Meredith; Arabella Poulson; Philip Bearcroft; Graeme Crossland; David M Baguley; John D Scott; Martin P Snead
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  46     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-26     Completed Date:  2005-03-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  663-8     Citation Subset:  IM    
Department of Pathology, University of Cambridge, Cambridge, UK.
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MeSH Terms
Alternative Splicing / genetics
Cells, Cultured
Collagen Type II / genetics*
DNA Mutational Analysis
Exons / genetics
Genes, Dominant
Linkage (Genetics)
RNA, Messenger / metabolism
Retinal Detachment / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/COL2A1 protein, human; 0/Collagen Type II; 0/RNA, Messenger

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