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

Yuchen Lin, Christine L. Xu, Mark P. Breazzano, Akemi J. Tanaka, Joseph Ryu, Sarah R. Levi, Ke Yao, Janet R. Sparrow, Stephen H. Tsang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)26-30
Number of pages5
JournalOphthalmic genetics
Volume41
Issue number1
DOIs
StatePublished - Jan 2 2020
Externally publishedYes

Keywords

  • KIZ
  • ciliopathy
  • disease progression
  • genetic testing
  • retinitis pigmentosa

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology
  • Genetics(clinical)

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