PMID- 33960280 OWN - NLM STAT- MEDLINE DCOM- 20220127 LR - 20230606 IS - 1744-5094 (Electronic) IS - 1381-6810 (Print) IS - 1381-6810 (Linking) VI - 42 IP - 4 DP - 2021 Aug TI - A novel KCNV2 mutation in a patient taking hydroxychloroquine associated with cone dystrophy with supernormal rod response. PG - 458-463 LID - 10.1080/13816810.2021.1920039 [doi] AB - BACKGROUND: Cone dystrophy with supernormal rod response (CDSRR) is a rare inherited retinal degeneration. A patient superimposed with medical conditions requiring use of hydroxychloroquine (HCQ) may obscure accurate diagnosis of CDSRR. Herein, we report a referral case for HCQ retinopathy screening. Comprehensive ophthalmic examinations, however, guided the diagnosis of CDSRR from a novel mutation in potassium voltage-gated channel modifier subfamily V member 2 (KCNV2) gene. MATERIALS AND METHODS: Comprehensive ophthalmic examinations were evaluated for two patients whose parents are first cousins. Direct sanger sequencing of KCNV2 was applied to confirm the mutation. RESULTS: A 38-year-old male proband was referred for HCQ retinopathy screening after taking HCQ for systemic lupus erythematosus (SLE). Fundus examination showed bull's eye pattern, and photoreceptor loss in the foveal region of both eyes was noted on spectral domain-optical coherence tomography (SD-OCT). The full-field electroretinography (ffERG) revealed a disproportionate increase in scotopic maximal response with implicit time delay, as well as universal cone dysfunction. Proband's 24-year-old sister had similar ffERG pattern in both eyes. Direct sanger sequencing of KCNV2 gene revealed a novel homozygous mutation c.280_281 insG (p.Ala94GlyfsTer278), confirming a diagnosis of CDSRR. CONCLUSIONS: We report a novel KCNV2 mutation in a consanguineous family. The unique ffERG features of CDSRR are pathognomonic and thus crucial in guiding clinicians toward genetic testing of the KCNV2 gene. Altogether, multimodal imaging, ffERG, and detailed history taking are important diagnostic tools for differentiating between acquired and inherited retinal disorders. FAU - Liu, Pei-Kang AU - Liu PK AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, New York, 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 - Ryu, Joseph AU - Ryu J AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, New York, USA. FAU - Yeh, Lung-Kun AU - Yeh LK AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Kuan-Jen AU - Chen KJ AUID- ORCID: 0000-0002-4994-8391 AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Tsang, Stephen H AU - Tsang SH AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, New York, USA. FAU - Liu, Laura AU - Liu L AD - Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Wang, Nan-Kai AU - Wang NK AUID- ORCID: 0000-0002-6277-9879 AD - Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, New York, USA. LA - eng GR - R21 AG050437/AG/NIA NIH HHS/United States GR - R01 EY031354/EY/NEI NIH HHS/United States GR - R01 EY018213/EY/NEI NIH HHS/United States GR - U01 EY030580/EY/NEI NIH HHS/United States GR - U54 OD020351/OD/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 - R24 EY028758/EY/NEI NIH HHS/United States GR - R01 EY024698/EY/NEI NIH HHS/United States GR - P30 EY019007/EY/NEI NIH HHS/United States PT - Case Reports PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210507 PL - England TA - Ophthalmic Genet JT - Ophthalmic genetics JID - 9436057 RN - 0 (Antirheumatic Agents) RN - 0 (KCNV2 protein, human) RN - 0 (Potassium Channels, Voltage-Gated) RN - 4QWG6N8QKH (Hydroxychloroquine) RN - Retinal Cone Dystrophy 3B SB - IM MH - Adult MH - Antirheumatic Agents/*adverse effects MH - Consanguinity MH - Electroretinography MH - Female MH - Frameshift Mutation/*genetics MH - Genetic Testing MH - Humans MH - Hydroxychloroquine/*adverse effects MH - Lupus Erythematosus, Systemic/drug therapy MH - Male MH - Phenotype MH - Potassium Channels, Voltage-Gated/*genetics MH - Retinal Cone Photoreceptor Cells/physiology MH - Retinal Rod Photoreceptor Cells/physiology MH - Retinitis Pigmentosa/*chemically induced/diagnosis/*genetics/physiopathology MH - Tomography, Optical Coherence MH - Young Adult PMC - PMC10234695 MID - NIHMS1900663 OTO - NOTNLM OT - Cone dystrophy with supernormal rod response (CDSRR) OT - KCNV2 OT - full-field electroretinography (ffERG) OT - hydroxychloroquine OT - sanger sequencing 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- 2021/05/08 06:00 MHDA- 2022/01/28 06:00 PMCR- 2023/06/01 CRDT- 2021/05/07 08:55 PHST- 2021/05/08 06:00 [pubmed] PHST- 2022/01/28 06:00 [medline] PHST- 2021/05/07 08:55 [entrez] PHST- 2023/06/01 00:00 [pmc-release] AID - 10.1080/13816810.2021.1920039 [doi] PST - ppublish SO - Ophthalmic Genet. 2021 Aug;42(4):458-463. doi: 10.1080/13816810.2021.1920039. Epub 2021 May 7.