High Frequency Of Submicroscopic Chromosomal Deletions in Patients with Idiopathic Congenital Eye Malformations

• Published in: American journal of ophthalmology 2011-06, Vol.151 (6), p.1087-1094.e45
• Main Authors: Balikova, Irina, de Ravel, Thomy, Ayuso, Carmen, Thienpont, Bernard, Casteels, Ingele, Villaverde, Cristina, Devriendt, Koenraad, Fryns, Jean-Pierre, Vermeesch, Joris Robert
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 16 - genetics; Comparative Genomic Hybridization; Cytogenetics; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; DNA Primers - chemistry; Eye Abnormalities - genetics; Eye Proteins - genetics; Female; Forkhead Transcription Factors - genetics; Genetic testing; Genetics; Grants; Homeodomain Proteins - genetics; Humans; Infant; Infant, Newborn; Male; Medical sciences; Mental retardation; Methods; Miscellaneous; Mutation; Ophthalmology; Otx Transcription Factors - genetics; Paired Box Transcription Factors - genetics; PAX6 Transcription Factor; Polymerase Chain Reaction; Repressor Proteins - genetics; Vesicular Transport Proteins - genetics
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2010.11.025

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.