LAUSR

ABSTRACT Background Uveal colobomata are eye defects that result from failure of the optic fissure of the neuroectoderm-derived optic cup to close between weeks 5–7 of fetal life. Mutations in YAP1 have previously been linked to uveal coloboma. We present the clinical features and genetic basis of a one-year-old male with bilateral uveal colobomata. Materials and methods Clinical features were gathered from an age-appropriate evaluation and retrospectively from clinical records. DNA samples were collected from the proband, his uncle (who also had coloboma), both parents, and one sibling. Whole-genome sequencing of the coding regions and intron-exon boundaries confirmed a mutation in the proband. These genetic findings were verified using the Sanger method of DNA sequencing. Results The proband is a male with congenital bilateral colobomata (iris/retina/nerve), reduced vision, nystagmus with null point, bilateral microcornea, right microphthalmia, possible mild right hemifacial microsomia, a tubular nose, possible spina bifida occulta, and astigmatism. Whole-genome sequencing confirmed a heterozygous YAP1 frameshift mutation NM_001130145.3:c.178dupG p.(Asp60GlyfsTer52) in the proband. This mutation was absent in all other tested family members. Conclusions We report a de novo mutation in YAP1 that likely results in nonsense-mediated decay. Given the association with YAP1 haploinsufficiency and colobomatous microphthalmia, this novel variant provides a molecular diagnosis for the proband. Further insight into YAP1 mutations may have implications in the prevention/treatment of uveal coloboma and other syndromic disorders.