title: A complex TFAP2A allele is associated with branchio-oculo-facial syndrome and inner ear malformation in a deaf child.
abstract: We present a 4-year-old girl with congenital profound sensorineural deafness associated with inner ear malformation (incomplete partition type II, enlarged vestibule, and enlarged vestibular aqueduct). The proposita also had pseudocleft lips, skin defects, auricle abnormalities, and unilateral multicystic dysplastic kidney, leading to the diagnosis of branchio-oculo-facial (BOF) syndrome. Mutation analysis of the TFAP2A gene showed a de novo deletion of 18 and insertion of 6 nucleotides, resulting in deletion of amino acids LPGARR and insertion of RI between amino acids 276 and 281. Altered amino acids are located within the basic DNA binding and dimerization domains of TFAP2A. Previously reported amino acid substitutions in TFAP2A involved only DNA binding domain in four patients with BOF syndrome who were not reported to have profound sensorineural deafness. Our report implies that the localization of mutations in TFAP2A might be responsible with the phenotypic findings in BOF syndrome.
authors.affiliation: Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey. mtekin@medicine.ankara.edu.tr
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.forename: Asli
authors.initials: A
authors.lastname: Sirmaci
authors.forename: Berrin
authors.initials: B
authors.lastname: Yüksel-Konuk
authors.forename: Suat
authors.initials: S
authors.lastname: Fitoz
authors.forename: Levent
authors.initials: L
authors.lastname: Sennaroğlu
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics*; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000235:genetics; D007758:Ear, Inner / Q000002:abnormalities*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D017434:Protein Structure, Tertiary; D011859:Radiography; D013701:Temporal Bone / Q000000981:diagnostic imaging; D050656:Transcription Factor AP-2 / Q000235:genetics*
chemical_list: C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2