title: De novo EDA mutations: Variable expression in two Egyptian families.
abstract: OBJECTIVE
  Mutations in the EDA gene, encoding the epithelial morphogen ectodysplasin-A, can result in different but overlapping phenotypes. Therefore the aim of the study was to search for etiological variations of EDA and other candidate genes in two unrelated Egyptian male children with sporadic non-syndromic tooth agenesis (NTA) and hypohidrotic ectodermal dysplasia (HED).
  
  
  METHODS
  Direct sequencing of the coding regions including exon-intron boundaries of EDA, MSX1, PAX9, WNT10A and EDAR was performed in probands and their available family members.
  
  
  RESULTS
  Two etiological mutations were found in the EDA coding region. The patient with NTA in both deciduous and permanent dentition was a carrier of a novel in-frame deletion situated in the short collagenous domain (c.663-680delTCCTCCTGGTCCTCAAGG, p.222-227delPPGPQG). The second mutation, located outside the minimal furin consensus motif (c.463C>T, p.Arg155Cys, rs132630312), was identified in the patient exhibiting all typical features of HED. The identified EDA mutations were not detected in probands' family members as well as in 188 unrelated control individuals. No pathogenic variants were found in the MSX1, PAX9, WNT10A and EDAR genes.
  
  
  CONCLUSIONS
  Our results increase the knowledge of the spectrum of EDA mutations and confirm that this gene is an important candidate gene for two developmental diseases sharing the common feature of the congenital lack of teeth. In addition, these results can support the hypothesis that X-linked HED and EDA-related NTA are the same disease with different degrees of severity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gaczkowska
authors.affiliation: Department of Medical Genetics, King Abdulaziz University, Jeddah, SA, Saudi Arabia; Department of Human Genetics, Medical Research Institute, Alexandria University, Egypt.
authors.forename: Ebtesam M
authors.initials: EM
authors.lastname: Abdalla
authors.affiliation: Department of Paediatric Dentistry, Faculty of Dentistry, Alexandria University, Egypt.
authors.forename: Karin M L
authors.initials: KM
authors.lastname: Dowidar
authors.affiliation: Department of Human Genetics, Medical Research Institute, Alexandria University, Egypt.
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Elhady
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Jagodzinski
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: amostowska@wp.pl.
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
mesh_terms: D000848:Anodontia / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000235:genetics; D053331:Ectodysplasins / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics; D004534:Egypt; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics; D008297:Male; D009154:Mutation; D051764:PAX9 Transcription Factor / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D051153:Wnt Proteins / Q000235:genetics
chemical_list: C506018:EDA protein, human; C506008:EDAR protein, human; D053331:Ectodysplasins; D053339:Edar Receptor; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; C484142:WNT10A protein, human; D051153:Wnt Proteins
keywords: EDA; Mutation; Tooth agenesis; XLHED