title: TFAP2A mutations result in branchio-oculo-facial syndrome.
abstract: Branchio-oculo-facial syndrome (BOFS) is a rare autosomal-dominant cleft palate-craniofacial disorder with variable expressivity. The major features include cutaneous anomalies (cervical, infra- and/or supra-auricular defects, often with dermal thymus), ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies. The molecular basis for this disorder is heretofore unknown. We detected a 3.2 Mb deletion by 500K SNP microarray in an affected mother and son with BOFS at chromosome 6p24.3. Candidate genes in this region were selected for sequencing on the basis of their expression patterns and involvement in developmental pathways associated with the clinical findings of BOFS. Four additional BOFS patients were found to have de novo missense mutations in the highly conserved exons 4 and 5 (basic region of the DNA binding domain) of the TFAP2A gene in the candidate deleted region. We conclude BOFS is caused by mutations involving TFAP2A. More patients need to be studied to determine possible genetic heterogeneity and to establish whether there are genotype-phenotype correlations.
authors.affiliation: Center for Human Genetics, Boston University School of Medicine, Boston, MA 02118-2526, USA. jmilunsk@bu.edu
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Milunsky
authors.forename: Tom A
authors.initials: TA
authors.lastname: Maher
authors.forename: Geping
authors.initials: G
authors.lastname: Zhao
authors.forename: Amy E
authors.initials: AE
authors.lastname: Roberts
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Stalker
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Zori
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Burch
authors.forename: Michele
authors.initials: M
authors.lastname: Clemens
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Smith
authors.forename: Angela E
authors.initials: AE
authors.lastname: Lin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D050656:Transcription Factor AP-2 / Q000235:genetics*
chemical_list: C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2