Missense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish. (December 2019)

• Record Type: Journal Article
• Authors: Toms, Maria; Dubis, Adam M.; Lim, Wei Sing; Webster, Andrew R.; Gorin, Michael B.; Moosajee, Mariya
• Is Part Of: Experimental eye research. Volume 189(2019)
• Publication Date: 2019-12
• Subjects: Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2019.107852
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Mutations in KCNJ13 are associated with two retinal disorders; Leber congenital amaurosis (LCA) and snowflake vitreoretinal degeneration (SVD). We describe a novel fibrovascular proliferation in the retina of two affected members of a KCNJ13 -related LCA family with a homozygous c.458C > T, p.(Thr153Ile) missense mutation. Optical coherence tomography retinal imaging of the kcnj13 mutant zebrafish ( obelix td15 c.502T > C, p.[Phe168Leu]) revealed a late onset retinal degeneration at 12 months, with retinal thinning and associated retinovascular changes, including increased vessel calibre and vitreous deposits. Both human and zebrafish variants are missense and located within the conserved transmembrane M2 protein domain, suggesting that disruption of this region may contribute to retinovascular changes as an additional feature to the previously described LCA phenotype. Close monitoring of other patients with similar mutations may be required to minimise the ensuing retinal damage. Highlights: Patients with KCNJ13 c.458C>T, p.(Thr153Ile) mutations were examined for retinovascular abnormalities. A novel fibrovascular proliferation was observed in the retina of two siblings with KCNJ13 -Leber congenital amaurosis. kcnj13 mutant zebrafish ( obelix td15 ) showed a retinal degeneration with associated retinovascular changes. Both human and zebrafish variants are missense and located within the transmembrane M2 protein domain. This retinovascular complication should be considered within the clinical spectrum of KCNJ13 -related retinal disease.