High frequency of submicroscopic chromosomal deletions in patients with idiopathic congenital eye malformations

Am J Ophthalmol. 2011 Jun;151(6):1087-1094.e45. doi: 10.1016/j.ajo.2010.11.025. Epub 2011 Feb 25.

Abstract

Purpose: 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.

Design: 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.

Publication types

  • Case Reports
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Deletion*
  • Chromosomes, Human, Pair 16 / genetics*
  • Comparative Genomic Hybridization
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Eye Abnormalities / genetics*
  • Eye Proteins / genetics*
  • Female
  • Forkhead Transcription Factors / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Otx Transcription Factors / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Polymerase Chain Reaction
  • Repressor Proteins / genetics*
  • Vesicular Transport Proteins / genetics*

Substances

  • DNA Primers
  • Eye Proteins
  • FOXC1 protein, human
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • OTX2 protein, human
  • Otx Transcription Factors
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins
  • VPS13B protein, human
  • Vesicular Transport Proteins