Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 5, 1178-1184, 17 April 2008
doi:10.1016/j.ajhg.2008.03.007
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Mutation in the Human Homeobox Gene NKX5-3 Causes an Oculo-Auricular Syndrome
Daniel F. Schorderet1, 2, 3, 
, 
, Olivia Nichini1, 2, Gaëlle Boisset1, 2, Bozena Polok1, Leila Tiab1, Hélène Mayeur4, Bahija Raji4, Gauillaume de la Houssaye4, Marc M. Abitbol4 and Francis L. Munier2, 5
1 Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland
2 Department of Ophthalmology, University of Lausanne, 1000 Lausanne, Switzerland
3 Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
4 CERTO – EA No 2502 du ministère de la recherche, Faculty of Medicine, 75015 Paris, France
5 Jules-Gonin Eye Hospital, 1004 Lausanne, Switzerland
Corresponding authorAbstract
Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (microcornea, microphthalmia, anterior-segment dysgenesis, cataract, coloboma of various parts of the eye, abnormalities of the retinal pigment epithelium, and rod-cone dystrophy) and a particular cleft ear lobule. Linkage analysis and mutation screening revealed in the first exon of the NKX5-3 gene a homozygous 26 nucleotide deletion, generating a truncating protein that lacked the complete homeodomain. Morpholino knockdown expression of the zebrafish nkx5-3 induced microphthalmia and disorganization of the developing retina, thus confirming that this gene represents an additional member implicated in axial patterning of the retina.
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