Communicated by Garry R. Cutting
VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: The first description of a VAX1 phenotype in humans†
Article first published online: 27 DEC 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 2, pages 364–368, February 2012
How to Cite
Slavotinek, A. M., Chao, R., Vacik, T., Yahyavi, M., Abouzeid, H., Bardakjian, T., Schneider, A., Shaw, G., Sherr, E. H., Lemke, G., Youssef, M. and Schorderet, D. F. (2012), VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: The first description of a VAX1 phenotype in humans. Hum. Mutat., 33: 364–368. doi: 10.1002/humu.21658
- Issue published online: 12 JAN 2012
- Article first published online: 27 DEC 2011
- Accepted manuscript online: 16 NOV 2011 10:33AM EST
- Manuscript Accepted: 9 NOV 2011
- Manuscript Received: 18 AUG 2011
- Eunice Kennedy Shriver National Institute of Child Health and Development at the National Institutes of Health (K08 HD053476 to A.S.; R01 EY017478 to G.L.)
- NIH/NCRR UCSF-CTSI (UL1 RR024131)
Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M. Hum Mutat 33:364–368, 2012. © 2011 Wiley Periodicals, Inc.