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B. L. Varsanyi, B. Wissinger, P. Enyedi, A. Farkas; Genotype Phenotype Correlation in Carriers of Mutations in KCNV2 Gene. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3090.
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© ARVO (1962-2015); The Authors (2016-present)
Cone dystrophy with supernormal rod-response (CDSRR) is an inherited retinal disorder characterized by seriously affected photopic (cone) function, increased scotopic maximal b-wave amplitudes and high b/a ratios in Ganzfeld electroretinography (GfERG). KCNV2, the gene responsible for this disease, encodes the modulatory Kv8.2 subunit of a voltage-gated potassium channel. The exact role of this subunit is still unclear in the pathophysiology of this cone dystrophy. The aim of our study was to analyze the GfERGs of heterozygous carriers of the mutant KCNV2 gene.
Parents and three siblings of a patient with CDSRR underwent detailed ophthalmological examination including Ganzfeld electroretinography (Roland Consult, Germany). Molecular genetic investigations included PCR amplification, sequencing of PCR products, SNP segregation analysis and qPCR for copy number determination, The patient is compound heterozygous for a large deletion (c.434_*30+154del, encompassing large parts of the gene) and a point mutation (c.442G>T, E148X) resulting in premature translation termination. Molecular genetic examinations were performed using direct sequencing and RT-PCR techniques.
Father and a brother of the index patient are heterozygous for the large deletion; mother and a sister are heterozygous for the point mutation. The two other siblings carry no mutation in the KCNV2 gene. All examined relatives have good visual function, photopic ERGs were normal. The carriers of the point mutation have moderately increased scotopic maximal b-wave amplitudes (628 ± 21.3 µV) and b/a ratios (above 1.8, mean 1.93 ± 0.17) compared to the other family members (560 ± 63.8 µV; 1.49 ± 0.17; analogous to the normal values).
The markedly altered electrophysiological responses of the carriers of the c.442G>T point mutations implies that in spite of the premature termination, the truncated Kv8.2 protein bears some dominant negative inhibitory effect on the voltage-gated potassium channel.
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