title: Characterization of a novel mutation in PAX9 gene in a family with non-syndromic dental agenesis.
abstract: BACKGROUND
  Dental agenesis is the most common developmental anomaly in man and may present either as an isolated trait or as part of a syndrome, such as ectodermal dysplasia. Until now, the underlying molecular pathogenic mechanisms responsible for dental agenesis are still largely unknown. Several genetic and molecular studies have demonstrated that at least 300 genes are involved in tooth formation and development, coding for specific transcriptional factors, receptors or growth factors that are expressed at specific developmental stages. Dental agenesis in this respect is believed to result from altered expression of one or more of these factors during initiation and early morphogenesis of the tooth germ, and the first actors identified were MSX1 and PAX9.
  
  
  METHODS
  In this study, we focalized on a Tunisian family with a non-syndromic autosomal dominant form of tooth agenesis. In order to screen for the eventual genetic cause of dental agenesis in this family we sequenced 4 genes; PAX9, WNT10A, MSX1 and AXIN2 using Sanger sequencing.
  
  
  RESULTS
  Direct Screening analysis of PAX9 gene, revealed a novel mutation p.Asp200Serfs*13. It consists of a duplication of 5 basepairs leading to a codon stop 13 position downstream. This novel mutation was found in all affected family members.
  
  
  CONCLUSIONS
  In this report, we present the first genetic study of a Tunisian family with a non-syndromic autosomal dominant form of tooth agenesis, in which we identified in PAX9 gene a novel mutation. It most likely results in nonsense mediated RNA decay and haploinsifficiency that reduce the transactivation capacity of PAX9.
authors.affiliation: Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Ibn Aljazzar street, 4031, Sousse, Tunisia. Electronic address: marwa.mastouri@gmail.com.
authors.forename: Marwa
authors.initials: M
authors.lastname: Haddaji Mastouri
authors.affiliation: Department of Restorative Dentistry, Endodontology and Oral Biology, Ghent University Hospital, 1P8 185 De Pintelaan, 9000 Ghent, Belgium. Electronic address: peter.decoster@ugent.be.
authors.forename: Peter
authors.initials: P
authors.lastname: De Coster
authors.affiliation: Department of Oral Surgery, Farhat Hached University Hospital, Ibn Aljazzar street, 4031, Sousse,Tunisia. Electronic address: aichazaghbani@yahoo.fr.
authors.forename: Aicha
authors.initials: A
authors.lastname: Zaghabani
authors.affiliation: Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Ibn Aljazzar street, 4031, Sousse, Tunisia. Electronic address: tsaoussen@yahoo.fr.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Trabelsi
authors.affiliation: Department of Orthodontics, Farhat Hached University Hospital, Ibn Aljazzar street, 4031, Sousse, Tunisia. Electronic address: mayyosra@hotmail.fr.
authors.forename: Yosra
authors.initials: Y
authors.lastname: May
authors.affiliation: Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Ibn Aljazzar street, 4031, Sousse, Tunisia. Electronic address: ali.saad@rns.tn.
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.affiliation: Department of Medical Genetics, MRB, 1st floor, Ghent University Hospital De Pintelaan 185, B-9000 Ghent, Belgium. Electronic address: paul.coucke@ugent.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.affiliation: Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Ibn Aljazzar street, 4031, Sousse, Tunisia. Electronic address: dorrahmida@yahoo.fr.
authors.forename: Dorra
authors.initials: D
authors.lastname: H'mida Ben Brahim
mesh_terms: D000848:Anodontia / Q000000981:diagnostic imaging / Q000235:genetics*; D002508:Cephalometry; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D051764:PAX9 Transcription Factor / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014416:Tunisia
chemical_list: D051764:PAX9 Transcription Factor
keywords: Dental agenesis; Frameshift mutations; PAX9 gene