Exome sequencing confirms ZNF408 mutations as a cause of familial retinitis pigmentosa

• Published in: Acta ophthalmologica (Oxford, England) Vol. 93; no. S255
• Main Authors: Habibi, I., Chebil, A., Kort, F., Munier, F., Schorderet, D., El Matri, L.
• Format: Journal Article
• Language: English
• Published: Malden Wiley Subscription Services, Inc 01.10.2015
• Subjects: Ophthalmology
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2015.0425

Purpose The aim of this study was to identify the gene causing retinitis pigmentosa (RP) in a Tunisian family. Methods Three members of a consanguineous Tunisian family were clinically examined and were given best‐corrected visual acuity (BCVA), slit lamp biomicroscopy, fundus photography and optical coherence tomography scanning (OCT) testing. Blood samples were collected for DNA extraction. Regions of homozygosity were further analyzed in the index case and whole exome sequencing was performed. All detected mutations in candidate genes were validated by Sanger sequencing. Results The phenotype was characterized by hemeralopia starting in the first decade of life. BCVA ranged from 20/100 to 20/40. Fundus examination revealed typical RP changes with bone spicule‐shaped pigment deposits in the mid periphery along with atrophy of the retina, narrowing of the vessels and waxy optic discs. Tomograms showed macular edema. They also had high myopia and posterior subcapsular cataract. Mutation analysis in the region of homozygosity identified a c.653‐1G>T mutation in the canonical splice site of exon 5 of the zinc finger protein 408 (ZNF408) gene. All three affected members were homozygous for this mutation. Conclusions So far, only two different mutations have been identified (Avila‐Fernandez et al, Hum Mol Genet. 2015). This family represents the third case of ZNF408 mutations and further expands the clinical spectrum ofmutations.