Exome Sequencing Identification of EP300 Mutation in a Proband with Coloboma and Imperforate Anus: Possible Expansion of the Phenotypic Spectrum of Rubinstein-Taybi Syndrome

Mol Syndromol. 2015 Jul;6(2):99-103. doi: 10.1159/000375542. Epub 2015 Mar 3.


Rubinstein-Taybi syndrome (RSTS) is a multisystem developmental disorder characterized by facial dysmorphisms, broad thumbs and halluces, growth retardation, and intellectual disability. In about 8% of RSTS cases, mutations are found in EP300. Previously, the EP300 mutation has been shown to cause the highly variable RSTS phenotype. Using exome sequencing, we identified a de novo EP300 frameshift mutation in a proband with coloboma, facial asymmetry and imperforate anus with minimal RSTS features. Previous molecular studies have demonstrated the importance of EP300 in oculogenesis, supporting the possibility that EP300 mutation may cause ocular coloboma. Since a wide phenotypic spectrum is well known in EP300-associated RSTS cases, the atypical phenotype identified in our proband may be an example of rare manifestations of RSTS.

Keywords: Coloboma; EP300 mutation; Imperforate anus; Rubinstein-Taybi syndrome.