PMID- 36384460 OWN - NLM STAT- MEDLINE DCOM- 20221121 LR - 20230426 IS - 1471-2415 (Electronic) IS - 1471-2415 (Linking) VI - 22 IP - 1 DP - 2022 Nov 16 TI - Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa. PG - 441 LID - 10.1186/s12886-022-02659-6 [doi] LID - 441 AB - BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene. CASE PRESENTATION: Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain-optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F. CONCLUSIONS: We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP. CI - (c) 2022. The Author(s). FAU - Chen, Nelson AU - Chen N AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, New York, NY, 10032, USA. AD - Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada. FAU - Lee, Hane AU - Lee H AD - Division of Medical Genetics, 3billion, Inc., Seoul, South Korea. FAU - Kim, Angela H AU - Kim AH AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, New York, NY, 10032, USA. AD - College of Medicine at the State University of New York at Downstate Medical Center, Brooklyn, NY, USA. FAU - Liu, Pei-Kang AU - Liu PK AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, New York, NY, 10032, USA. AD - Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Kang, Eugene Yu-Chuan AU - Kang EY AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Tseng, Yun-Ju AU - Tseng YJ AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, New York, NY, 10032, USA. FAU - Seo, Go Hun AU - Seo GH AD - Division of Medical Genetics, 3billion, Inc., Seoul, South Korea. FAU - Khang, Rin AU - Khang R AD - Division of Medical Genetics, 3billion, Inc., Seoul, South Korea. FAU - Liu, Laura AU - Liu L AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Kuan-Jen AU - Chen KJ AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Wu, We-Chi AU - Wu WC AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Hsiao, Meng-Chang AU - Hsiao MC AD - Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA. FAU - Wang, Nan-Kai AU - Wang NK AUID- ORCID: 0000-0002-6277-9879 AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, New York, NY, 10032, USA. wang.nankai@gmail.com. AD - Vagelos College of Physicians and Surgeons, Columbia University, New York, USA. wang.nankai@gmail.com. LA - eng GR - P30 EY019007/EY/NEI NIH HHS/United States PT - Case Reports PT - Journal Article DEP - 20221116 PL - England TA - BMC Ophthalmol JT - BMC ophthalmology JID - 100967802 RN - 0 (Cadherins) RN - Usher Syndrome, Type IF SB - IM MH - Humans MH - *Usher Syndromes/diagnosis/genetics MH - *Retinitis Pigmentosa/diagnosis/genetics MH - Retina MH - Cadherins/genetics PMC - PMC9670441 OTO - NOTNLM OT - Case report OT - Congenital hearing loss OT - Loss of function OT - Nonsense-mediated decay OT - PCDH15 OT - Protocadherin-15 OT - Syndromic retinitis pigmentosa OT - Usher syndrome type 1F (USH1F) COIS- The authors report no conflicts of interest and are alone responsible for the content and writing of this article. EDAT- 2022/11/18 06:00 MHDA- 2022/11/22 06:00 PMCR- 2022/11/16 CRDT- 2022/11/17 09:42 PHST- 2022/08/09 00:00 [received] PHST- 2022/10/29 00:00 [accepted] PHST- 2022/11/17 09:42 [entrez] PHST- 2022/11/18 06:00 [pubmed] PHST- 2022/11/22 06:00 [medline] PHST- 2022/11/16 00:00 [pmc-release] AID - 10.1186/s12886-022-02659-6 [pii] AID - 2659 [pii] AID - 10.1186/s12886-022-02659-6 [doi] PST - epublish SO - BMC Ophthalmol. 2022 Nov 16;22(1):441. doi: 10.1186/s12886-022-02659-6.