Abstract
Purpose :
The Kizuna (KIZ) gene encodes a centrosomal protein and was first reported to be associated with inherited retinal dystrophy (IRD) in 2014. Since then only six cases have been reported worldwide. Here we aimed to characterize genotype and phenotype in what to our knowledge is the biggest cohort of patients with KIZ-associated IRD reported to date.
Methods :
Medical records of KIZ patients were retrospectively reviewed, and genetic, clinical, imaging, and electrophysiological data were analyzed.
Results :
We identified 18 patients with KIZ mutations: 16 (ages 13-66) have a homozygous p.R76* mutation and 2 (ages 42&50) were compound heterozygous for p.R76* and c.3G>A (p.M1?). From the homozygous group, 13/16 were of Ashkenazi Jewish (AJ) descent, 2 from Morocco and 1 from Turkey. Both compound heterozygous patients were from a mixed background (Bulgaria-Macedonia & Poland-Iraq).
Clinical data was available for 14 patients: 8/14 patients (ages 21-66) had good visual acuity (≥20/40) in at least one eye up until the last examination and 8/12 patients (ages 25-66) manifested cataracts, commonly posterior subcapsular.
Fundus imaging, available in 11 patients, showed two main phenotypes: 6 patients (5 Homo & 1 het, ages 13-66) manifested relatively mild disease with minimal funduscopic changes even at advanced age, although FAF revealed hypoautofluorescent spots and a macular hyperautofluorescent ring. Five other homozygous patients showed more aggressive disease with funduscopic features of classic RP, including bone spicule-like pigmentation, attenuation of retinal vessels and optic disc pallor.
On OCT, 4/8 patients (2 mild and 2 with RP-like phenotype) showed a mild ERM, and only one (in the mild group) had cystoid changes. Visual fields showed progressive constriction, reduced to less than 10 degrees by the age of 30 in 7/9 patients. FFERG was still recordable in patients up until 62 years of age, with a rod>cone dystrophy pattern. Interestingly, the Arden ratio on EOG testing was reduced in all 6 patients who performed this test to values lower than predicted by the extent of FFERG loss.
Conclusions :
KIZ mutations are an uncommon cause of IRD worldwide, but are not rare among AJ, with a 1:79 carrier rate for the p.R76* mutation. Fundus findings are often mild and can be missed. In an AJ patient, FFERG testing showing a rod>cone pattern of injury and an EOG Arden ratio that is lower than expected may suggest KIZ as the cause of disease.
This is a 2021 ARVO Annual Meeting abstract.