Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes

Khanh Nhat Tran-Viet, Vincent Soler, Valencia Quiette, Caldwell Powell, Tammy Yanovitch, Ravikanth Metlapally, Xiaoyan Luo, Elias Nicholas Katsanis, Erica Nading, Terri L. Young

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Purpose: Stickler syndrome is an arthro-ophthalmopathy with phenotypic overlap with Wagner syndrome. The common Stickler syndrome type I is inherited as an autosomal dominant trait, with causal mutations in collagen type II alpha 1 (COL2A1). Wagner syndrome is associated with mutations in versican (VCAN), which encodes for a chondroitin sulfate proteoglycan. A three-generation Caucasian family variably diagnosed with either syndrome was screened for sequence variants in the COL2A1 and VCAN genes. Methods: Genomic DNA samples derived from saliva were collected from all family members (six affected and four unaffected individuals). Complete sequencing of COL2A1 and VCAN was performed on two affected individuals. Direct sequencing of remaining family members was conducted if the discovered variants followed segregation. Results: A base-pair substitution (c.258C>A) in exon 2 of COL2A1 cosegregated with familial disease status. This known mutation occurs in a highly conserved site that causes a premature stop codon (p.C86X). The mutation was not seen in 1,142 ethnically matched control DNA samples. Conclusions: Premature stop codons in COL2A1 exon 2 lead to a Stickler syndrome type I ocular-only phenotype with few or no systemic manifestations. Mutation screening of COL2A1 exon 2 in families with autosomal dominant vitreoretinopathy is important for accurate clinical diagnosis.

Original languageEnglish (US)
Pages (from-to)759-766
Number of pages8
JournalMolecular vision
Volume19
StatePublished - Apr 5 2013

ASJC Scopus subject areas

  • Ophthalmology

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