Communicated by Maria Rita Passos-Bueno
Mutation in Brief
EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally†
Article first published online: 15 JUL 2009
© 2009 Wiley-Liss, Inc.
Volume 30, Issue 10, pages E946–E955, October 2009
How to Cite
Abe, Y., Oka, A., Mizuguchi, M., Igarashi, T., Ishikawa, S., Aburatani, H., Yokoyama, S., Asahara, H., Nagao, K., Yamada, M. and Miyashita, T. (2009), EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally. Hum. Mutat., 30: E946–E955. doi: 10.1002/humu.21094
- Issue published online: 28 SEP 2009
- Article first published online: 15 JUL 2009
- Manuscript Accepted: 30 JUN 2009
- Manuscript Received: 2 APR 2009
- The Japan Society for the Promotion of Science (to KN). Grant Number: 19790750
- Cited By
- middle interhemispheric variant
Holoprosencephaly (HPE) is the most common congenital malformation of the developing human forebrain, in which the two cerebral hemispheres fail to separate to various degrees. Although pathological mutations have been identified in up to nine genes, a number of other genes as well as environmental factors are likely to be involved in HPE. Here, we describe a case with the middle interhemispheric variant, a milder variant of HPE, carrying a deletion of ∼10.4 Mb at 6q22.31-q23.2, which includes the EYA4 gene. EYA4 is one of four vertebrate orthologs of the Drosophila melanogaster gene, eyes absent. EYA4 was co-immunoprecipitated with SIX3, the product of one of the known HPE genes. Moreover, the EYA4 protein was observed to be recruited to the nucleus by the nuclear protein SIX3 under a confocal microscope. EYA4 is a transcriptional coactivator, and was shown to cooperate with transcription factor SIX3 by reporter gene assays. These results demonstrate physical and functional association between EYA4 and SIX3, suggesting that EYA4 is a novel candidate gene of HPE, whose haploinsufficiency leads to HPE through the compromised function of SIX3. © 2009 Wiley-Liss, Inc.