PMID- 32052671 OWN - NLM STAT- MEDLINE DCOM- 20210311 LR - 20220716 IS - 1744-5094 (Electronic) IS - 1381-6810 (Print) IS - 1381-6810 (Linking) VI - 41 IP - 1 DP - 2020 Feb TI - Progressive RPE atrophy and photoreceptor death in KIZ-associated autosomal recessive retinitis pigmentosa. PG - 26-30 LID - 10.1080/13816810.2020.1723116 [doi] AB - 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 mum 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. FAU - Lin, Yuchen AU - Lin Y AUID- ORCID: 0000-0002-2679-2849 AD - Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. AD - Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China. FAU - Xu, Christine L AU - Xu CL AD - Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. FAU - Breazzano, Mark P AU - Breazzano MP AD - Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Ophthalmology, New York University School of Medicine, New York, New York, USA. FAU - Tanaka, Akemi J AU - Tanaka AJ AD - Department of Pathology & Cell Biology, Institute of Human Nutrition, and Columbia Stem Cell Initiative, Columbia University, New York, New York, USA. FAU - Ryu, Joseph AU - Ryu J AD - Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. FAU - Levi, Sarah R AU - Levi SR AD - Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. FAU - Yao, Ke AU - Yao K AD - Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China. FAU - Sparrow, Janet R AU - Sparrow JR AD - Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Pathology & Cell Biology, Institute of Human Nutrition, and Columbia Stem Cell Initiative, Columbia University, New York, New York, USA. FAU - Tsang, Stephen H AU - Tsang SH AUID- ORCID: 0000-0001-9082-2427 AD - Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. AD - Department of Pathology & Cell Biology, Institute of Human Nutrition, and Columbia Stem Cell Initiative, Columbia University, New York, New York, USA. LA - eng GR - R01 EY024091/EY/NEI NIH HHS/United States GR - R21 AG050437/AG/NIA NIH HHS/United States GR - R01 EY018213/EY/NEI NIH HHS/United States GR - U01 EY030580/EY/NEI NIH HHS/United States GR - R01 EY026682/EY/NEI NIH HHS/United States GR - R24 EY027285/EY/NEI NIH HHS/United States GR - P30 CA013696/CA/NCI NIH HHS/United States GR - R01 EY024698/EY/NEI NIH HHS/United States GR - P30 EY019007/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200213 PL - England TA - Ophthalmic Genet JT - Ophthalmic genetics JID - 9436057 RN - 0 (Cell Cycle Proteins) RN - 0 (KIZ protein, human) SB - IM MH - Adult MH - Atrophy/complications MH - Cell Cycle Proteins/*genetics MH - Cell Death MH - Choroidal Neovascularization/*complications MH - Female MH - Genes, Recessive MH - Humans MH - Male MH - Middle Aged MH - *Mutation MH - Pedigree MH - Pigment Epithelium of Eye/metabolism/*pathology MH - Prognosis MH - Retinal Rod Photoreceptor Cells/metabolism/*pathology MH - Retinitis Pigmentosa/*etiology/pathology MH - Young Adult PMC - PMC9070555 MID - NIHMS1632303 OTO - NOTNLM OT - KIZ OT - ciliopathy OT - disease progression OT - genetic testing OT - retinitis pigmentosa COIS- Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. EDAT- 2020/02/14 06:00 MHDA- 2021/03/12 06:00 PMCR- 2022/05/05 CRDT- 2020/02/14 06:00 PHST- 2020/02/14 06:00 [pubmed] PHST- 2021/03/12 06:00 [medline] PHST- 2020/02/14 06:00 [entrez] PHST- 2022/05/05 00:00 [pmc-release] AID - 10.1080/13816810.2020.1723116 [doi] PST - ppublish SO - Ophthalmic Genet. 2020 Feb;41(1):26-30. doi: 10.1080/13816810.2020.1723116. Epub 2020 Feb 13.