Journal
MOLECULAR GENETICS & GENOMIC MEDICINE
Volume 9, Issue 10, Pages -Publisher
WILEY
DOI: 10.1002/mgg3.1795
Keywords
compound heterozygous mutations; cone dystrophy with supernormal rod response; exome sequence; KCNV2
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Funding
- National Natural Science Foundation of China [31970698]
- Sichuan Science and Technology Program [2019YFS0272]
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This study identified KCNV2 gene mutations in a Chinese CDSRR family, expanding the spectrum of mutations associated with CDSRR. In vitro functional experiments showed that mutated alleles led to the failure of Kv8.2 proteins to express and interact with Kv2.1 protein, suggesting a potential mechanism for the etiology of CDSRR.
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 he 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.
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