Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family

Abstract Background Cone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive retinal disorder characterized by myopia, dyschromatopsia, nyctalopia, photophobia, and nystagmus. CDSRR is caused by mutations in KCNV2, the gene encoding for an electrically silent Kv subunit (Kvs) n...

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Autores principales:	Man Liu, Yingchuan Zhu, Lian Huang, Wenhao Jiang, Na Wu, Yue Song, Yilu Lu, Yongxin Ma
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	compound heterozygous mutations cone dystrophy with supernormal rod response exome sequence KCNV2 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fd71fed7edfc4471980aa6289eac83ec
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spelling	oai:doaj.org-article:fd71fed7edfc4471980aa6289eac83ec2021-11-10T16:39:23ZCompound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family2324-926910.1002/mgg3.1795https://doaj.org/article/fd71fed7edfc4471980aa6289eac83ec2021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1795https://doaj.org/toc/2324-9269Abstract Background Cone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive retinal disorder characterized by myopia, dyschromatopsia, nyctalopia, photophobia, and nystagmus. CDSRR is caused by mutations in KCNV2, the gene encoding for an electrically silent Kv subunit (Kvs) named Kv8.2. Methods A Chinese CDSRR family was recruited. Complete ophthalmology clinical examinations were performed to clarify the phenotype. Genetic examination was underwent using whole exome sequencing (WES). In addition, a candidate gene was validated by Sanger sequencing. Expression analysis in vitro including immunoblotting, quantitative real‐time PCR (qRT‐PCR), and co‐immunoprecipitation experiments was performed to investigate the pathogenic mechanism of the identified gene variants. Results WES identified two KCNV2 heterozygous mutations from the proband. Sanger sequencing validated that the patient's parents had, respectively, carried those two mutations. Further in vitro functional experiments indicated that the mutated alleles had led the Kv8.2 proteins to fail in expressing and interacting with the Kv2.1 protein, respectively. Conclusions This study expanded the KCNV2 mutation spectrum. It can also be deduced that CDSRR has a broad heterogeneity. It is further confirmed that the inability expression of Kv8.2 proteins and the failure of Kv8.2 proteins to interact with Kv2.1 may have accounted for the etiology of CDSRR based on previous studies and this study.Man LiuYingchuan ZhuLian HuangWenhao JiangNa WuYue SongYilu LuYongxin MaWileyarticlecompound heterozygous mutationscone dystrophy with supernormal rod responseexome sequenceKCNV2GeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	compound heterozygous mutations cone dystrophy with supernormal rod response exome sequence KCNV2 Genetics QH426-470
spellingShingle	compound heterozygous mutations cone dystrophy with supernormal rod response exome sequence KCNV2 Genetics QH426-470 Man Liu Yingchuan Zhu Lian Huang Wenhao Jiang Na Wu Yue Song Yilu Lu Yongxin Ma Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family
description	Abstract Background Cone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive retinal disorder characterized by myopia, dyschromatopsia, nyctalopia, photophobia, and nystagmus. CDSRR is caused by mutations in KCNV2, the gene encoding for an electrically silent Kv subunit (Kvs) named Kv8.2. Methods A Chinese CDSRR family was recruited. Complete ophthalmology clinical examinations were performed to clarify the phenotype. Genetic examination was underwent using whole exome sequencing (WES). In addition, a candidate gene was validated by Sanger sequencing. Expression analysis in vitro including immunoblotting, quantitative real‐time PCR (qRT‐PCR), and co‐immunoprecipitation experiments was performed to investigate the pathogenic mechanism of the identified gene variants. Results WES identified two KCNV2 heterozygous mutations from the proband. Sanger sequencing validated that the patient's parents had, respectively, carried those two mutations. Further in vitro functional experiments indicated that the mutated alleles had led the Kv8.2 proteins to fail in expressing and interacting with the Kv2.1 protein, respectively. Conclusions This study expanded the KCNV2 mutation spectrum. It can also be deduced that CDSRR has a broad heterogeneity. It is further confirmed that the inability expression of Kv8.2 proteins and the failure of Kv8.2 proteins to interact with Kv2.1 may have accounted for the etiology of CDSRR based on previous studies and this study.
format	article
author	Man Liu Yingchuan Zhu Lian Huang Wenhao Jiang Na Wu Yue Song Yilu Lu Yongxin Ma
author_facet	Man Liu Yingchuan Zhu Lian Huang Wenhao Jiang Na Wu Yue Song Yilu Lu Yongxin Ma
author_sort	Man Liu
title	Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family
title_short	Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family
title_full	Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family
title_fullStr	Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family
title_full_unstemmed	Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family
title_sort	compound heterozygous kcnv2 variants contribute to cone dystrophy with supernormal rod responses in a chinese family
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/fd71fed7edfc4471980aa6289eac83ec
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Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family

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