title: High frequency of submicroscopic chromosomal deletions in patients with idiopathic congenital eye malformations.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the clinical usefulness of the array comparative genomic hybridization technique for the genetic analysis of patients with congenital ocular malformations.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  This was a multicenter study. Samples were collected from 37 patients with negative results for the routine diagnostic work-up, including normal karyotype and mutation analysis of appropriate genes. Samples from both parents also were tested. High-resolution genome-wide Agilent 244K oligoarray (Agilent Technologies) was applied. Confirmation of the results was obtained with independent techniques.
  
  
  RESULTS
  Causal deletions were identified in 5 (13%) patients, affecting OTX2, FOXC1 and VPS13B (COH1), the downstream regulatory region of PAX6, and a 1,5 Megabases de novo deletion on chromosome 16.
  
  
  CONCLUSIONS
  This high frequency of causal submicroscopic chromosomal aberrations in patients with congenital ocular malformation warrants implementation of array comparative genomic hybridization in the diagnostic work-up of these patients. Moreover, this screening technique broadens the phenotypic and mutational spectrum associated with genes known to cause congenital ocular malformation.
authors.affiliation: Centre for Human Genetics, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Irina
authors.initials: I
authors.lastname: Balikova
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Bernard
authors.initials: B
authors.lastname: Thienpont
authors.forename: Ingele
authors.initials: I
authors.lastname: Casteels
authors.forename: Cristina
authors.initials: C
authors.lastname: Villaverde
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005124:Eye Abnormalities / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051857:Otx Transcription Factors / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005136:Eye Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins