Lisa A. Schimmenti and June de la Cruz contributed equally to this work.
Article first published online: 24 SEP 2002
Copyright © 2003 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 116A, Issue 3, pages 215–221, 30 January 2003
How to Cite
Schimmenti, L. A., de la Cruz, J., Lewis, R. A., Karkera, J.D., Manligas, G. S., Roessler, E. and Muenke, M. (2003), Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia. Am. J. Med. Genet., 116A: 215–221. doi: 10.1002/ajmg.a.10884
This article was prepared by a group consisting of both United States Government employees and non-United States Government employees, and as such is subject to 117 U.S.C. Sed. 105.
- Issue published online: 26 DEC 2002
- Article first published online: 24 SEP 2002
- Manuscript Accepted: 9 JUL 2002
- Manuscript Received: 1 FEB 2002
- Division of Intramural Research, NHGRI
- UCLA Academic Senate
- Research to Prevent Blindness
- Mae and Angelo Schiraldi
- NIH-NHLBI. Grant Number: K08 HL03515
- sonic hedgehog;
Ocular (uveoretinal) colobomas occur in one in 10,000 individuals and present a substantive cause of congenital poor vision. The genetic bases of most forms of uveoretinal coloboma are elusive; mutations in PAX2 are found in only a few cases of coloboma of the retina and optic nerve that occur with renal anomalies as part of the renal-coloboma syndrome (MIM#120330; #167409). From experimental data that upstream expression of sonic hedgehog (SHH) controls Pax2 expression in mice and zebrafish, and from clinical experience that colobomas are observed frequently in patients with holoprosencephaly, we hypothesized that SHH could be a candidate for non-syndromic ocular colobomas (NSOC). We identified a three-generation family in which both a proband and his mother presented with iris and uveoretinal colobomas without optic nerve involvement. A novel 24 bp deletion in the gene SHH was identified in these affected family members, and cosegregated with the phenotype. This is the first report of the association of SHH mutations and uveoretinal coloboma. © 2002 Wiley-Liss, Inc.