Human genetic diseases and Wnt signaling components
There are many cases of genetic diseases due to mutations in Wnt signaling components. Among these are several where multiple Wnt signaling components have been found as mutated in families. These diseases include abnormalities in bone density, tooth development and the retina. Another example is Robinow syndrome, associated with mutations in three different Wnt signaling components: ROR2 (Van Bokhoven et al, 2000) , WNT5A and DVL1.
The table lists many of these diseases and the genes mutated.
See for reviews:
Moon, RT et al, WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 2004 Sep;5(9):691-701
Clevers, H and Nusse, R. Wnt/β-Catenin Signaling and Disease.Cell. 2012 Jun 8;149(6):1192-205.
Anastas, JN and Moon, RT WNT signalling pathways as therapeutic targets in cancer.Nature Rev Cancer 13 2013:11-26
Gene |
Disease |
References |
| APC | Polyposis coli | Kinzler et al 1991, Nishisho et al 1991 |
| LRP5 |
Bone Density defects Vascular defects in the eye (Osteoperosis-pseudoglioma Syndrome, OPPG) |
Gong, 2001 Little, 2002, Boyden, 2002 |
| LRP5 | Familial Exudative Vitreoretinopathy | Toomes et al, 2004 |
| LRP6 | early coronary disease | Mani, 2007 |
| LRP6 | Late onset Alzheimer | De Ferrari 2007 |
| LRP6 | Autosomal-Dominant Oligodontia | (Massink, 2015) |
| FZD4 |
Familial Exudative Vitreoretinopathy: retinal angiogenesis |
Robitaille, 2002 |
| FZD9 | Williams Syndrome | |
| Norrin | Familial Exudative Vitreoretinopathy | Xu et al, 2004 |
| WNT1 | Osteogenesis imperfecta | |
| Tetra-Amelia | Niemann et al 2004 | |
| WNT4 | Mullerian-duct regression and virilization | Biason-Lauber 2004 |
| WNT4 | SERKAL syndrome | Mandel, 2008 |
| WNT5A | Robinow syndrome | (Person 2010) |
| WNT5B | Type II diabetes | Kanazawa 2004 |
| WNT7A | Fuhrmann syndrome | Woods 2006 |
| WNT10A | Odonto-onycho-dermal dysplasia | Adaimy, 2007 |
| WNT10B | Obesity | Christodoulides 2006 |
| WNT10B | Split-Hand/Foot Malformation | Ugur, 2008 |
| WNT10B | Oligodontia | Yu, 2016 |
| WNT16 | Bone density | Zheng et al, 2012 |
| DVL1 | Robinow Syndrome. | (White et al, 2015) |
| AXIN1 | caudal duplication | Oates, 2006 |
| TCF7L2 (TCF4) | Type II diabetes | |
| AXIN2 | Tooth agenesis | Lammli et al, 2004 Marvin et al, 2011 |
| WTX | Wilms tumor | Major, 2007, Rivera, 2007 |
| WTX | skeletal dysplasia | Jenkins, 2009 |
| PORCN | Focal dermal hypoplasia | Grzeschik 2007 |
| RSPO1 | Palmoplantar hyperkeratosis | Parma 2006 |
| RSPO2 | Tetra-amelia | Szenker-Ravi, 2018 |
| RSPO4 | autosomal recessive anonychia | Bergmann 2006, Blaydon 2006 |
| LGR4 | Bone Density defects | Styrkarsdottir et al, 2013 |
| VANGL1 | Neural tube defects | Kibar, 2007 |
| SOST | Sclerosteosis and Van Buchem disease | |
| SFRP4 | Pyle's disease (Bone density) | |
| ROR2 | Robinow syndrome | |
| WLS (Wntless) | Pleiotropic Multiorgan Condition |
