title: Nonsyndromic oligodontia : Does the Tooth Agenesis Code (TAC) enable prediction of the causative mutation?
abstract: OBJECTIVE
  The literature suggests an association between phenotype and causative mutation in nonsyndromic oligodontia. Thus, the present study was designed to verify this hypothesis in a consecutive cohort of patients.
  
  
  METHODS
  All patients with nonsyndromic oligodontia who had been treated at the study center (Department of Orthodontics, University of Giessen, Germany) over the period 1986-2013 were contacted. Candidates were included only if at least one more family member had hypo- or oligodontia (i.e., without regard to the number of congenitally missing teeth). A total of 20 patients were included. After evaluating the dental status of each participant, the Tooth Agenesis Code (TAC) was applied. On this basis, a tentative diagnosis was made to predict which gene (MSX1, AXIN2, EDA, or PAX9) was likely to show mutation. Afterwards this hypothesis was confirmed or rejected by analyzing a saliva sample for mutation of the predicted gene. If confirmed, any available family members were also genetically analyzed.
  
  
  RESULTS
  Based on their TAC scores and sums, gene mutations were predicted for MXS1 in 11, AXIN2 in 3, EDA in 6, and PAX9 in none of the patients. The evaluation of MSX1 yielded variants in 4 of 11 cases, all of which were classified as nonpathogenic since they were not considered as functional mutations. The evaluation of EDA yielded a pathogenic exon-7 mutation in 2 of 6 patients, both being brothers with different TAC scores; the same mutation, which represents a novel missense mutation, was also found in other members of the same family. The evaluation of AXIN2 yielded variants in 3 of 3 cases, all of which were classified as nonpathogenic.
  
  
  CONCLUSIONS
  Our findings obtained in consecutive patients with nonsyndromic oligodontia did not reveal any clinically relevant associations between oligodontia phenotype (based on TAC) and causative mutations for nonsyndromic oligodontia.
authors.affiliation: Department of Orthodontics, University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany. niko.c.bock@dentist.med.uni-giessen.de.
authors.forename: Niko C
authors.initials: NC
authors.lastname: Bock
authors.affiliation: Private Practice, Lübeck, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lenz
authors.affiliation: Department of Orthodontics, University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Ruiz-Heiland
authors.affiliation: Department of Orthodontics, University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ruf
mesh_terms: D000293:Adolescent; D000848:Anodontia / Q000453:epidemiology* / Q000235:genetics*; D058070:Asymptomatic Diseases / Q000453:epidemiology; D060466:Axin Protein / Q000235:genetics*; D015984:Causality; D002648:Child; D053331:Ectodysplasins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D051764:PAX9 Transcription Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; C506018:EDA protein, human; D053331:Ectodysplasins; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human
keywords: Agenesis; Familial; Genotype; Hypodontia; Mutation; Phenotype