%L discovery10179384
%I BMJ
%O © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
%A Thales AC de Guimaraes
%A Michalis Georgiou
%A Anthony G Robson
%A Kaoru Fujinami
%A Ajoy Vincent
%A Fadi Nasser
%A Samer Khateb
%A Omar A Mahroo
%A Nikolas Pontikos
%A Maurício E Vargas
%A Alberta AHJ Thiadens
%A Emanuel R de Carvalho
%A Xuan-Than-An Nguyen
%A Gavin Arno
%A Yu Fujinami-Yokokawa
%A Xiao Liu
%A Kazushige Tsunoda
%A Takaaki Hayashi
%A Belén Jiménez-Rolando
%A Maria Inmaculada Martin-Merida
%A Almudena Avila-Fernandez
%A Ester Carreño Salas
%A Blanca Garcia-Sandoval
%A Carmen Ayuso
%A Dror Sharon
%A Susanne Kohl
%A Rachel M Huckfeldt
%A Eyal Banin
%A Mark E Pennesi
%A Arif O Khan
%A Bernd Wissinger
%A Andrew R Webster
%A Elise Heon
%A Camiel JF Boon
%A Eberhard Zrenner
%A Michel Michaelides
%J British Journal of Ophthalmology
%X BACKGROUND/AIMS: 

To investigate genotype–phenotype associations in patients withKCNV2retinopathy.


METHODS: 
Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination ofKCNV2variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared.


RESULTS: 

Ninety-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.

CONCLUSIONS: 

Patients 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.
%T KCNV2-associated retinopathy: genotype–phenotype correlations – KCNV2 study group report 3
%D 2023