The authors declare no conflict of interest.
Whole-genome copy number variation analysis in anophthalmia and microphthalmia
Article first published online: 17 JUN 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Special Issue: Variant
Volume 84, Issue 5, pages 473–481, November 2013
How to Cite
Whole-genome copy number variation analysis in anophthalmia and microphthalmia., , , , , , , , .
These authors contributed equally to this work.
- Issue published online: 17 OCT 2013
- Article first published online: 17 JUN 2013
- Accepted manuscript online: 22 MAY 2013 03:26PM EST
- Manuscript Revised: 17 MAY 2013
- Manuscript Accepted: 17 MAY 2013
- Manuscript Received: 24 FEB 2013
- National Institutes of Health. Grant Numbers: R01EY015518, R21DC010912
- Children's Hospital of Wisconsin
- Clinical and Translational Science Award. Grant Number: 1UL1RR031973
- copy number variation;
Anophthalmia/microphthalmia (A/M) represent severe developmental ocular malformations. Currently, mutations in known genes explain less than 40% of A/M cases. We performed whole-genome copy number variation analysis in 60 patients affected with isolated or syndromic A/M. Pathogenic deletions of 3q26 (SOX2) were identified in four independent patients with syndromic microphthalmia. Other variants of interest included regions with a known role in human disease (likely pathogenic) as well as novel rearrangements (uncertain significance). A 2.2-Mb duplication of 3q29 in a patient with non-syndromic anophthalmia and an 877-kb duplication of 11p13 (PAX6) and a 1.4-Mb deletion of 17q11.2 (NF1) in two independent probands with syndromic microphthalmia and other ocular defects were identified; while ocular anomalies have been previously associated with 3q29 duplications, PAX6 duplications, and NF1 mutations in some cases, the ocular phenotypes observed here are more severe than previously reported. Three novel regions of possible interest included a 2q14.2 duplication which cosegregated with microphthalmia/microcornea and congenital cataracts in one family, and 2q21 and 15q26 duplications in two additional cases; each of these regions contains genes that are active during vertebrate ocular development. Overall, this study identified causative copy number mutations and regions with a possible role in ocular disease in 17% of A/M cases.