Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia

Human MutationVolume 33, Issue 1 p. 86-90 Brief Report Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia† Marine R.-C. Kraus, Marine R.-C. Kraus Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, SwitzerlandSearch for more papers by this authorSéverine Clauin, Séverine Clauin Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, Paris, FranceSearch for more papers by this authorYvan Pfister, Yvan Pfister Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, SwitzerlandSearch for more papers by this authorMassimo Di Maïo, Massimo Di Maïo Département de Pédiatrie, CHU Poitiers, Poitiers, FranceSearch for more papers by this authorTim Ulinski, Tim Ulinski Département de Néphrologie Pédiatrique, Université Pierre et Marie Curie, AP-HP, Hôpital Armand Trousseau, Paris, FranceSearch for more papers by this authorDaniel Constam, Daniel Constam Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, SwitzerlandSearch for more papers by this authorChristine Bellanné-Chantelot, Corresponding Author Christine Bellanné-Chantelot [email protected] Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, Paris, France Christine Bellanné-Chantelot, Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, 75651 Paris Cedex 13, France Anne Grapin-Botton, Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, SwitzerlandSearch for more papers by this authorAnne Grapin-Botton, Corresponding Author Anne Grapin-Botton [email protected] Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, Switzerland Both authors contributed equally to this work. Christine Bellanné-Chantelot, Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, 75651 Paris Cedex 13, France Anne Grapin-Botton, Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, SwitzerlandSearch for more papers by this author Marine R.-C. Kraus, Marine R.-C. Kraus Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, SwitzerlandSearch for more papers by this authorSéverine Clauin, Séverine Clauin Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, Paris, FranceSearch for more papers by this authorYvan Pfister, Yvan Pfister Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, SwitzerlandSearch for more papers by this authorMassimo Di Maïo, Massimo Di Maïo Département de Pédiatrie, CHU Poitiers, Poitiers, FranceSearch for more papers by this authorTim Ulinski, Tim Ulinski Département de Néphrologie Pédiatrique, Université Pierre et Marie Curie, AP-HP, Hôpital Armand Trousseau, Paris, FranceSearch for more papers by this authorDaniel Constam, Daniel Constam Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, SwitzerlandSearch for more papers by this authorChristine Bellanné-Chantelot, Corresponding Author Christine Bellanné-Chantelot [email protected] Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, Paris, France Christine Bellanné-Chantelot, Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, 75651 Paris Cedex 13, France Anne Grapin-Botton, Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, SwitzerlandSearch for more papers by this authorAnne Grapin-Botton, Corresponding Author Anne Grapin-Botton [email protected] Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, Switzerland Both authors contributed equally to this work. Christine Bellanné-Chantelot, Département de Génétique, Université Pierre et Marie Curie, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, 75651 Paris Cedex 13, France Anne Grapin-Botton, Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, SwitzerlandSearch for more papers by this author First published: 15 September 2011 https://doi.org/10.1002/humu.21610Citations: 55 † Communicated by Michel Goossens Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract 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. Citing Literature Supporting Information Additional Supporting information may be found in the online version of this article Filename Description humu_21610_sm_SuppInfo.pdf748.3 KB Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume33, Issue1January 2012Pages 86-90 RelatedInformation