Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients
Open Access
- 24 February 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in European Journal of Human Genetics
- Vol. 18 (8), 872-880
- https://doi.org/10.1038/ejhg.2010.23
Abstract
Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P90% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome.This publication has 34 references indexed in Scilit:
- Missense and nonsense mutations in the alternatively-spliced exon 2 ofCOL2A1cause the ocular variant of Stickler syndromeHuman Mutation, 2007
- A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype–phenotype correlations in type XI collagenopathiesAmerican Journal of Medical Genetics Part A, 2007
- A New Autosomal Recessive Form of Stickler Syndrome Is Caused by a Mutation in the COL9A1 GeneAmerican Journal of Human Genetics, 2006
- High efficiency of mutation detection in type 1 stickler syndrome using a two-stage approach: vitreoretinal assessment coupled with exon sequencing for screening COL2A1Human Mutation, 2006
- The phenotypic spectrum in patients with arginine to cysteine mutations in the COL2A1 geneJournal of Medical Genetics, 2005
- Occurrence of deletion of a COL2A1 allele as the mutation in Stickler syndrome shows that a collagen type II dosage effect underlies this syndromeHuman Mutation, 2002
- A single amino acid substitution (G103D) in the type II collagen triple helix produces Kniest dysplasiaHuman Molecular Genetics, 1994
- The type II collagenopathies: A spectrum of chondrodysplasiasEuropean Journal of Pediatrics, 1994
- Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms.Proceedings of the National Academy of Sciences of the United States of America, 1989
- Probabilistic prediction in patient management and clinical trialsStatistics in Medicine, 1986