%0 Journal Article
%T Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele.
%A de Guimaraes TAC
%A Lai F
%A Colombatti R
%A Sato G
%A Rizzo R
%A Kalitzeos A
%A Michaelides M
%J Ophthalmic Genet
%V 0
%N 0
%D 2024 Mar 8
%M 38454848
%F 1.274
%R 10.1080/13816810.2024.2324046
%X <B>UNASSIGNED: </B>Disease-causing variants in the KCNV2 gene are associated with "cone dystrophy with supernormal rod responses," a rare autosomal recessive retinal dystrophy. There is no previous report of hypomorphic variants in the disease.<BR><B>UNASSIGNED: </B>Medical history, genetic testing, ocular examination, high-resolution retinal imaging including adaptive optics scanning light ophthalmoscopy (AOSLO), and functional assessments.<BR><B>UNASSIGNED: </B>A 16-year-old male with mild cone-rod dystrophy presented with reduced central vision and photophobia. Genetic testing showed two variants in KCNV2, c.614_617dupAGCG (p.207AlafsTer166) and c.854T>G (p.Met285Arg), the latter which was previously considered benign. Electrophysiological assessment revealed the pathognomic electroretinogram waveforms associated with KCNV2-retinopathy. Optical coherence tomography showed discrete focal ellipsoid zone disruption, while fundus autofluorescence was normal. Non-waveguiding cones corresponding to areas of loss of photoreceptor integrity were visible on adaptive optics scanning light ophthalmoscopy. Retinal sensitivity and fixation were relatively preserved, with a demonstrable deterioration after 14 months of follow-up.<BR><B>UNASSIGNED: </B>We provide functional and structural evidence that the variant M285R is disease-causing if associated with a loss-of-function variant. To the best of our knowledge, this is the first hypomorphic allele reported in KCNV2.