Both authors contributed equally to this work.
Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia†
Article first published online: 31 OCT 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 1, pages 86–90, January 2012
How to Cite
Kraus, M. R.-C., Clauin, S., Pfister, Y., Di Maïo, M., Ulinski, T., Constam, D., Bellanné-Chantelot, C. and Grapin-Botton, A. (2012), Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia. Hum. Mutat., 33: 86–90. doi: 10.1002/humu.21610
Communicated by Michel Goossens
- Issue published online: 14 DEC 2011
- Article first published online: 31 OCT 2011
- Accepted manuscript online: 15 SEP 2011 01:58PM EST
- Manuscript Accepted: 29 AUG 2011
- Manuscript Received: 8 JUL 2011
- Ecole Polytechnique Fédérale de Lausanne (to D.C. and A.G.B.)
- Swiss National Science Foundation (CRSI133_1306662 [to D.C. and A.G.B.])
- renal cysts;
Bicaudal C homologue 1 (Bicc1) knockout in mice causes polycystic kidney disease and pancreas development defects, including a reduction in insulin-producing β-cells and ensuing diabetes. We therefore screened 137 patients with renal abnormalities or association of early-onset diabetes and renal disease for genetic alterations in BICC1. We identified two heterozygous mutations, one nonsense in the first K Homology (KH) domain and one missense in the sterile alpha motif (SAM) domain. In mice, Bicc1 blocks canonical Wnt signaling, mostly via its SAM domain. We show that the human BICC1, similar to its mouse counterpart, blocks canonical Wnt signaling. The nonsense mutation identified results in a complete loss of Wnt inhibitory activity. The point mutation in the SAM domain has a similar effect to a complete SAM domain deletion, resulting in a 22% loss of activity. Hum Mutat 33:86–90, 2012. © 2011 Wiley Periodicals, Inc.