title: A novel TFAP2A mutation in familial Branchio-Oculo-Facial Syndrome with predominant ocular phenotype.
abstract: BACKGROUND
  Branchio-Oculo-Facial Syndrome (BOFS) is a rare autosomal dominant congenital disorder defined by branchial defects, ocular anomalies and craniofacial malformations, including variable degrees of cleft lip with or without cleft palate. In addition, temporal bone anomalies, renal and ectodermal manifestations can be present. Mutations in the TFAP2A gene have been reported in patients with BOFS, prompting phenotype-genotype studies because of the variable clinical spectrum.
  
  
  METHODS
  We report on a family (a mother, her daughter and son) with BOFS and significant variability in clinical expression. The daughter presents predominantly with an ocular phenotype of unilateral microphthalmia and bilateral chorioretinal colobomas, whereas her brother is more severely affected contrasting with the paucisymptomatic mother. TFAP2A molecular analysis revealed a novel frameshift mutation.
  
  
  CONCLUSIONS
  We confirm the wide clinical spectrum of BOFS. The importance of upper lip examination in mild and paucisymptomatic cases is underlined. TFAP2A mutation spectrum is discussed and broadened by the report of the second frameshift mutation in this gene.
  
  
  CONCLUSIONS
  Patients with BOFS and predominant ocular phenotypes can be underdiagnosed. In such cases, upper lip examination can be of important diagnostic value. TFAP2A analysis provides diagnostic confirmation and improves genetic counselling.
authors: Centre de Référence pour les Affections Rares en Génétique Ophtalmologique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. k.aliferis@gmail.com
authors: Konstantinos
authors: K
authors: Aliferis
authors: Corinne
authors: C
authors: Stoetzel
authors: Valérie
authors: V
authors: Pelletier
authors: Sophie
authors: S
authors: Hellé
authors: Karine
authors: K
authors: Angioï-Duprez
authors: Jacqueline
authors: J
authors: Vigneron
authors: Bruno
authors: B
authors: Leheup
authors: Vincent
authors: V
authors: Marion
authors: Hélène
authors: H
authors: Dollfus
mesh_terms: D000293:Adolescent; D019280:Branchio-Oto-Renal Syndrome / Q000175:diagnosis / Q000235:genetics*; D002829:Choroid / Q000002:abnormalities; D003103:Coloboma / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D008297:Male; D008850:Microphthalmos / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D012160:Retina / Q000002:abnormalities; D050656:Transcription Factor AP-2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2