TABLE 1.
Wnt and Shh pathway components mutated in human diseases with dental pathology.
Gene mutated | Pathway effect | Disease | References |
APC | Wnt hyperactivation | - Gardner syndrome, Familial Adenomatous Polyposis 1 (MIM 175100) | Half et al., 2009; Siriwardena et al., 2009 |
- Odontogenic carcinoma. | |||
AXIN2 | Wnt hyperactivation | Familial, non-syndromic hypodontia/tooth agenesis | Lammi et al., 2004; Mostowska et al., 2006; Yu et al., 2019 |
CTNNB1 | Wnt hyperactivation | - Ameloblastoma. | Sekine et al., 2002, 2003; Kawabata et al., 2005; Siriwardena et al., 2009; Brown et al., 2014; Yukimori et al., 2017 |
- Odontogenic carcinoma. | |||
- Calcifying odontogenic cysts. | |||
- Adamantinomatous craniopharyngioma. | |||
DKK1 | Wnt hyperactivation | Familial, non-syndromic tooth agenesis | Liu et al., 2012; Dinckan et al., 2018; Yu et al., 2019 |
DVL1 | Wnt inactivation | Robinow syndrome, autosomal dominant 2 (MIM 616331) | White et al., 2015 |
DVL3 | Wnt inactivation | Robinow syndrome, autosomal dominant 3 (MIM 616894) | White et al., 2016 |
FZD2 | Wnt inactivation (non-canonical) | Omodysplasia 2 (MIM 164745); Robinow syndrome-like | Nagasaki et al., 2018; White et al., 2018 |
GLI2 | Shh inactivation | Holoprosencephaly (9) with solitary median maxillary incisor (MIM 610829) | Roessler et al., 2003 |
GLI3 | Shh inactivation | Familial, non-syndromic hypodontia/tooth agenesis | Liu et al., 2012 |
KREMEN1 | Wnt hyperactivation | Ectodermal dysplasia 13, hair/tooth type (MIM 617392) | Issa et al., 2016; Dinckan et al., 2018 |
LRP4 | Wnt hyperactivation | Cenani-Lenz syndrome with dental anomalies (MIM 212780) | Li et al., 2010 |
LRP6 | Wnt inhibition | Familial, non-syndromic tooth agenesis | Massink et al., 2015; Dinckan et al., 2018; Yu et al., 2019 |
NXN | Wnt inactivation (non-canonical) | Robinow syndrome, autosomal recessive 2 (MIM 618529) | White et al., 2018 |
PORCN | Wnt inhibition | Focal Dermal Hypoplasia (MIM 305600) | Bornholdt et al., 2009; Froyen et al., 2009 |
PTCH1 | Shh activation | - Ameloblastoma. - Basal cell nevus syndrome with odontogenic keratocysts (MIM 601309 and 109400). | Kawabata et al., 2005; Guo et al., 2013; Shimada et al., 2013 |
PTCH2 | Shh activation | Basal cell nevus syndrome with odontogenic keratocysts (MIM 603673 and 109400) | Fujii et al., 2013 |
ROR2 | Wnt inactivation (non-canonical) | Robinow syndrome, autosomal recessive 1 (OMIM 268310) | Afzal et al., 2000; van Bokhoven et al., 2000; Mazzeu et al., 2007 |
SHH | Shh inhibition | Holoprosencephaly (3) with solitary median maxillary incisor (MIM 147250) | Nanni et al., 2001; Lami et al., 2013 |
SMO | Shh activation | Ameloblastoma | Brown et al., 2014; Sweeney et al., 2014 |
SUFU | Shh activation | Basal cell nevus syndrome with odontogenic keratocysts (MIM 607035 and 109400) | Pastorino et al., 2009; Shimada et al., 2013 |
WNT10A | Wnt inhibition | - Familial, non-syndromic tooth agenesis | Bohring et al., 2009; van den Boogaard et al., 2012; Arte et al., 2013; Song et al., 2014; Dinckan et al., 2018; Yu et al., 2019 |
- Odonto-onycho-dermal dysplasia (MIM 257980) | |||
- Schöpf-Schulz-Passarge syndrome (MIM 224750) | |||
WNT10B | Wnt inhibition | Familial, non-syndromic tooth agenesis | Yu et al., 2016, 2019 |
WNT5A | Wnt inactivation (non-canonical) | Robinow syndrome, autosomal dominant 1 (MIM 180700) | Person et al., 2010; Roifman et al., 2015 |