title: Deletions within COL11A1 in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA).
abstract: BACKGROUND
  COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the COL11A1, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown.
  
  
  METHODS
  We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone.
  
  
  CONCLUSIONS
  Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of COL11A1 should include assays capable of detecting both large and small deletions, in addition to exon sequencing.
authors.affiliation: East Anglian Regional Genetics Laboratory, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK.
authors.forename: Raymon
authors.initials: R
authors.lastname: Vijzelaar
authors.forename: Sarah
authors.initials: S
authors.lastname: Waller
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Errami
authors.forename: Alan
authors.initials: A
authors.lastname: Donaldson
authors.forename: Teresa
authors.initials: T
authors.lastname: Lourenco
authors.forename: Marcia
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Vivienne
authors.initials: V
authors.lastname: McConnell
authors.forename: Gregory
authors.initials: G
authors.lastname: Fincham
authors.forename: Martin
authors.initials: M
authors.lastname: Snead
authors.forename: Allan
authors.initials: A
authors.lastname: Richards
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D024161:Collagen Type XI / Q000172:deficiency / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D009154:Mutation; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D020255:Vitreous Detachment / Q000175:diagnosis / Q000235:genetics*
chemical_list: C574182:COL11A1 protein, human; D024161:Collagen Type XI