title: Involvement of and interaction between WNT10A and EDA mutations in tooth agenesis cases in the Chinese population.
abstract: BACKGROUND
  Dental agenesis is the most common, often heritable, developmental anomaly in humans. Although WNT10A gene mutations are known to cause rare syndromes associated with tooth agenesis, including onycho-odontodermal dysplasia (OODD), Schöpf-Schulz-Passarge syndrome (SSPS), hypohidrotic ectodermal dysplasia (HED), and more than half of the cases of isolated oligodontia recently, the genotype-phenotype correlations and the mode of inheritance of WNT10A mutations remain unclear. The phenotypic expression with WNT10A mutations shows a high degree of variability, suggesting that other genes might function with WNT10A in regulating ectodermal organ development. Moreover, the involvement of mutations in other genes, such as EDA, which is also associated with HED and isolated tooth agenesis, is not clear. Therefore, we hypothesized that EDA mutations interact with WNT10A mutations to play a role in tooth agenesis. Additionally, EDA, EDAR, and EDARADD encode signaling molecules in the Eda/Edar/NF-κB signaling pathways, we also checked EDAR and EDARADD in this study.
  
  
  METHODS
  WNT10A, EDA, EDAR and EDARADD were sequenced in 88 patients with isolated oligodontia and 26 patients with syndromic tooth agenesis. The structure of two mutated WNT10A and two mutated EDA proteins was analyzed.
  
  
  RESULTS
  Digenic mutations of both WNT10A and EDA were identified in 2 of 88 (2.27%) isolated oligodontia cases and 4 of 26 (15.38%) syndromic tooth agenesis cases. No mutation in EDAR or EDARADD gene was found.
  
  
  CONCLUSIONS
  WNT10A and EDA digenic mutations could result in oligodontia and syndromic tooth agenesis in the Chinese population. Moreover, our results will greatly expand the genotypic spectrum of tooth agenesis.
authors: Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
authors: Huiying
authors: H
authors: He
authors: Dong
authors: D
authors: Han
authors: Hailan
authors: H
authors: Feng
authors: Hong
authors: H
authors: Qu
authors: Shujuan
authors: S
authors: Song
authors: Baojing
authors: B
authors: Bai
authors: Zhenting
authors: Z
authors: Zhang
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D053331:Ectodysplasins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D016415:Sequence Alignment; D014071:Tooth Abnormalities / Q000175:diagnosis / Q000235:genetics*; D051153:Wnt Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; C484142:WNT10A protein, human; D051153:Wnt Proteins