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Progressive RPE atrophy and photoreceptor death in KIZ-associated autosomal recessive retinitis pigmentosa

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posted on 2020-02-13, 10:40 authored by Yuchen Lin, Christine L. Xu, Mark P. Breazzano, Akemi J. Tanaka, Joseph Ryu, Sarah R. Levi, Ke Yao, Janet R. Sparrow, Stephen H. Tsang

Background: To evaluate the long-term progression of autosomal recessive retinitis pigmentosa (RP) due to mutations in KIZ using multimodal imaging and a quantitative analytical approach.

Methods: Whole exome sequencing (WES) and targeted capture sequencing were used to identify mutation. Fundus photography, short-wavelength autofluorescence (SW-AF), spectral-domain optical coherence tomography (SD-OCT) imaging, and electroretinography (ERG) were analyzed. Serial measurements of peripheral retinal pigment epithelium (RPE) atrophy area with SW-AF, as well as the ellipsoid zone (EZ) width using SD-OCT were performed.

Results: Two homozygous variants in KIZ—a c.226C>T mutation as well as a previously unreported c.119_122delAACT mutation—were identified in four unrelated patients. Fundus examination and ERG revealed classic rod-cone dysfunction, and SD-OCT demonstrated outer retinal atrophy with centrally preserved EZ line. SW-AF imaging revealed hyperautofluorescent rings with surrounding parafoveal, mid-peripheral and widespread loss of autofluorescence. The RPE atrophy area increased annually by 4.9%. Mean annual exponential rates of decline for KIZ patients were 8.5% for visual acuity and 15.9% for 30 Hz Flicker amplitude. The average annual reduction distance of the EZ distance was 66.5 μm per year.

Conclusions: RPE atrophy progresses along with a loss of photoreceptors, and parafoveal RPE hypoautofluorescence is commonly seen in KIZ-associated RP patients. KIZ-associated RP is an early-onset severe rod-cone dystrophy.

Funding

YCL is supported by the China Scholarship Council (NO.201806320164). Jonas Children’s Vision Care is supported by National Institutes of Health 5P30CA013696, R24EY027285, R01EY018213, R01EY024698, R01EY026682, R01EY024091, R21AG050437, U01EY030580, the Schneeweiss Stem Cell Fund, New York State [C029572], the Foundation Fighting Blindness New York Regional Research Center Grant [C-NY05-0705-0312], Nancy & Kobi Karp, The Rosenbaum Family Foundation, the Gebroe Family Foundation, Alcon Research Institute, the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA.

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