| First Author | Lourenço D | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 4 | Pages | 1597-602 |
| PubMed ID | 21220346 | Mgi Jnum | J:168242 |
| Mgi Id | MGI:4887500 | Doi | 10.1073/pnas.1010257108 |
| Citation | Lourenco D, et al. (2011) Loss-of-function mutation in GATA4 causes anomalies of human testicular development. Proc Natl Acad Sci U S A 108(4):1597-602 |
| abstractText | Approximately 1 of every 250 newborns has some abnormality of genital and/or gonadal development. However, a specific molecular cause is identified in only 20% of these cases of disorder of sex development (DSD). We identified a family of French origin presenting with 46,XY DSD and congenital heart disease. Sequencing of the ORF of GATA4 identified a heterozygous missense mutation (p.Gly221Arg) in the conserved N-terminal zinc finger of GATA4. This mutation was not observed in 450 ancestry-matched control individuals. The mutation compromised the ability of the protein to bind to and transactivate the anti-Mullerian hormone (AMH) promoter. The mutation does not interfere with the direct protein-protein interaction, but it disrupts synergistic activation of the AMH promoter by GATA4 and NR5A1. The p.Gly221Arg mutant protein also failed to bind to a known protein partner FOG2 that is essential for gonad formation. Our data demonstrate the key role of GATA4 in human testicular development. |
