Missense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish
- Toms, M., Dubis, A.M., Lim, W.S., Webster, A.R., Gorin, M.B., Moosajee, M.
- Experimental Eye Research 189: 107852 (Journal)
- Registered Authors
- MeSH Terms
- Aged, 80 and over
- DNA Mutational Analysis
- Disease Models, Animal
- Fluorescein Angiography/methods
- Fundus Oculi
- Leber Congenital Amaurosis/genetics*
- Leber Congenital Amaurosis/metabolism
- Leber Congenital Amaurosis/pathology
- Middle Aged
- Mutation, Missense*
- Potassium Channels, Inwardly Rectifying/genetics*
- Potassium Channels, Inwardly Rectifying/metabolism
- Protein Domains
- Retinal Degeneration/genetics*
- Retinal Degeneration/metabolism
- Retinal Degeneration/pathology
- Tomography, Optical Coherence/methods
- Young Adult
- 31647904 Full text @ Exp. Eye. Res.
Toms, M., Dubis, A.M., Lim, W.S., Webster, A.R., Gorin, M.B., Moosajee, M. (2019) Missense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish. Experimental Eye Research. 189:107852.
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 (obelixtd15 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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes