| First Author | Abe Y | Year | 2009 |
| Journal | Hum Mutat | Volume | 30 |
| Issue | 10 | Pages | E946-55 |
| PubMed ID | 19606496 | Mgi Jnum | J:212800 |
| Mgi Id | MGI:5582166 | Doi | 10.1002/humu.21094 |
| Citation | Abe Y, et al. (2009) EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally. Hum Mutat 30(10):E946-55 |
| abstractText | 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 approximately 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. |
