Abstract
Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population.
Highlights
Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity
Funduscopy revealed typical retinitis pigmentosa (RP) changes with macular atrophy in F10 affected members suffering from photophobia; onset of symptoms was reported to occur during the first decade of life, with typical RP changes and normal macula
PDE6B was reported by several groups as one of the causative gene associated with autosomal recessive RP (arRP), including previous studies of consanguineous Tunisian families[16,17,18,19]
Summary
Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele These results confirm the involvement of a large number of genes in RD in the Tunisian population. Retinal dystrophies (RD) are a heterogeneous group of diseases in which the photoreceptor and RPE cells of the retina degenerate, leading to partial or complete blindness and affecting approximately 1 in 2500–3500 individuals[1]. Stargardt disease is a juvenile macular degeneration characterized by central vision loss[3] This group of rare genetic disorders shows substantial clinical and genetic overlaps with high genetic heterogeneity involving more than 220 genes identified so far (https://sph.uth.edu/retnet/). Different gene products are involved in many cellular functions and fall into four categories: proteins directly involved in the phototransduction cascade, genes encoding proteins responsible for the structure and polarity of the photoreceptors, genes encoding proteins of the visual cycle, and regulatory genes (such as transcription and splicing factors)[2]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
