Ocular manifestations of branchio-oculo-facial syndrome: report of a novel mutation and review of the literature

Abstract

Purpose: To report unusual ocular manifestations of branchio-oculo-facial syndrome (BOFS) caused by a novel mutation in activating enhancer binding protein 2 alpha (TFAP2A).

Methods: Full ophthalmological evaluation and direct sequencing of TFAP2A.

Results: A 10-year-old girl with unusual ocular manifestations of BOFS such as elliptical shaped microcornea and a novel de novo TFAP2A mutation was identified.

Conclusions: This report expands the ocular phenotypic spectrum of BOFS and adds to the small number of reported TFAP2A mutations.

Figure 1

Clinical photographs of the patient. Facial appearance with the typical pseudocleft of the upper lip is shown in A. Microcornea, inferonasal coloboma, and cataract are shown in B and C. Lateral facial profile is shown in D.

Figure 2

A novel mutation in TFAP2A. Sequence chromatogram of the patient is shown in A and B (forward and reverse) and that of her parents in C and D (forward only) with the c.763A>T mutation indicated by a red asterisk. Protein alignment across species in E shows very strong conservation of the R255 residue which is indicated by the red arrow.

Figure 3

Summary of previously reported TFAP2A mutations. A schematic of the TFAP2A gene is shown in A along with the genomic location of previously reported mutations. B and C show two different isoforms of the protein encoded by TFAP2A (AP2) along with the location of previously reported mutations at the protein level. The mutation in the current study is indicated by red asterisk. PG: proline/glutamine rich domain, B: basic DNA binding domain, HSH: helix span helix domain.