Genomic imbalances detected by array-CGH in patients with syndromal ocular developmental anomalies

Eur J Hum Genet. 2012 May;20(5):527-33. doi: 10.1038/ejhg.2011.233. Epub 2012 Jan 11.

Abstract

In 65 patients, who had unexplained ocular developmental anomalies (ODAs) with at least one other birth defect and/or intellectual disability, we performed oligonucleotide comparative genome hybridisation-based microarray analysis (array-CGH; 105A or 180K, Agilent Technologies). In four patients, array-CGH identified clinically relevant deletions encompassing a gene known to be involved in ocular development (FOXC1 or OTX2). In four other patients, we found three pathogenic deletions not classically associated with abnormal ocular morphogenesis, namely, del(17)(p13.3p13.3), del(10)(p14p15.3), and del(16)(p11.2p11.2). We also detected copy number variations of uncertain pathogenicity in two other patients. Rearranged segments ranged in size from 0.04 to 5.68 Mb. These results show that array-CGH provides a high diagnostic yield (15%) in patients with syndromal ODAs and can identify previously unknown chromosomal regions associated with these conditions. In addition to their importance for diagnosis and genetic counselling, these data may help identify genes involved in ocular development.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosome Aberrations
  • Comparative Genomic Hybridization
  • Eye Abnormalities / genetics*
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Dosage
  • Genome, Human*
  • Humans
  • Male
  • Otx Transcription Factors / genetics
  • Syndrome

Substances

  • FOXC1 protein, human
  • Forkhead Transcription Factors
  • OTX2 protein, human
  • Otx Transcription Factors