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. 2008 May;82(5):1171-7.
doi: 10.1016/j.ajhg.2008.03.005.

TFAP2A mutations result in branchio-oculo-facial syndrome

Affiliations

TFAP2A mutations result in branchio-oculo-facial syndrome

Jeff M Milunsky et al. Am J Hum Genet. 2008 May.

Erratum in

  • Am J Hum Genet. 2009 Feb;84(2):301.

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.

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Figures

Figure 1
Figure 1
500K SNP Microarray in BOFS Family 1 A 3.2 Mb deletion of 704 SNPs at 6p24.3 is shown with the UCSC genes inserted above the deletion.
Figure 2
Figure 2
Chromosome 6p24.3 Deletion in BOFS Family 1 (A) Microsatellite marker D6S309 showing absence of maternal allele (BOFS patient 1a) in her affected child (BOFS patient 1b) confirming the chromosome 6p deletion. (B) MLPA confirmation of TFAP2A gene deletion with two different intragenic probes (exons 5 and 6).
Figure 3
Figure 3
Sequence Chromatogram of TFAP2A Missense Mutations Numbering is according to NCBI: NC_000006.
Figure 4
Figure 4
Evolutionary Conservation of the Amino Acids in the TFAP2A Gene Altered in BOFS Patients Note the highly conserved amino acids from Homo sapiens through Ciona intestinalis in exons 4 and 5 of the TFAP2A gene.

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