Concurrent novel mutations in PAX3 and CFAP410 in a patient with Waardenburg syndrome type 1 associated with Retinitis Pigmentosa.

Background: Waardenburg syndrome (WS) is an auditory-pigmentary syndrome characterized by hair pigmentary abnormalities, pigmentary abnormalities of the iris, and congenital hearing loss. Type 1 associated with dystopia canthorum is caused by mutations in PAX3 gene which codes for DNA-binding transcription factor involved in neural crest border induction at the neural plate.

Methods: A 41-year-old male patient of consanguineous Egyptian parents presenting with progressive nyctalopia and field constriction underwent complete ophthalmological examination. Additionally, color fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) of the macula, full field electroretinogram (ERG), visual field perimetry and B-scans were obtained. Whole-exome sequencing (WES) was performed from a peripheral blood sample followed by bioinformatics analysis.

Results: A novel mutation in PAX3 gene c.688C>A was identified by WES consistent with a diagnosis of Waardenburg syndrome (WS) type 1. Further bioinformatic analysis of WES raw data identified another novel mutation in CFAP410 c.293C>T confirming the associated RP diagnosis.

Conclusion: To the best of our knowledge, this is the first report of RP in a WS patient. We are reporting novel mutations in PAX3 and CFAP410 genes and expanding number of cases of non-syndromic retinal degeneration in CFAP410- associated retinopathy.