Journal Article

KCNV2-associated retinopathy: genotype–phenotype correlations – KCNV2 study group report 3

Fujinami-Yokokawa, Yu, Heon, Elise, Garcia-Sandoval, Blanca, Arno, Gavin, Ayuso, Carmen, Liu, Xiao, Pontikos, Nikolas, Salas, Ester Carreño, Wissinger, Bernd, Zrenner, Eberhard, Khateb, Samer, de Guimaraes, Thales A C, Kohl, Susanne, Vincent, Ajoy, Sharon, Dror, Tsunoda, Kazushige, Webster, Andrew R, Avila-Fernandez, Almudena, Carvalho, Emanuel R de, Pennesi, Mark E, Fujinami, Kaoru, Nguyen, Xuan-Than-An, Thiadens, Alberta A H J, Nasser, Fadi, Martin-Merida, Maria Inmaculada, Jiménez-Rolando, Belén, Georgiou, Michalis, Hayashi, Takaaki, Banin, Eyal, Boon, Camiel J F, Khan, Arif O, Huckfeldt, Rachel M, Robson, Anthony G, Mahroo, Omar A, Vargas, Maurício E, Michaelides, Michel

2024

Overview

Background/aimsTo investigate genotype–phenotype associations in patients with KCNV2 retinopathy.MethodsReview of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared.ResultsNinety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants.ConclusionsPatients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Age / Child / Child, Preschool / Clinical science / Clinical trials / DNA Mutational Analysis / Dystrophy / Electrophysiology / Electroretinography / Female / Genetic Association Studies / Genetics / Genotype & phenotype / Humans / Imaging / Male / Mutation, Missense / Patients / Potassium / Potassium Channels, Voltage-Gated - genetics / Proteins / Retina / Retina - physiopathology / Retinal Diseases - diagnosis / Retinal Diseases - genetics / Retinal Diseases - physiopathology / Retrospective Studies / Software / Tomography, Optical Coherence / Variance analysis / Visual acuity / Visual Acuity - physiology