Molecular characteristics of four Japanese cases with KCNV2 retinopathy

Report of novel disease-causing variants

Kaoru Fujinami, Kazushige Tsunoda, Natsuko Nakamura, Yu Kato, Toru Noda, Kei Shinoda, Kaoru Tomita, Tetsuhisa Hatase, Tomoaki Usui, Masakazu Akahori, Takeshi Itabashi, Takeshi Iwata, Yoko Ozawa, Kazuo Tsubota, Yozo Miyake

Research output: Contribution to journalArticle

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Abstract

Purpose: To describe the molecular characteristics of four Japanese patients with cone dystrophy with supernormal rod responses (CDSRR). Methods: Four individuals with a clinical and electrophysiological diagnosis of CDSRR were ascertained. The pathognomonic findings of the full-field electroretinograms (ERGs) included a decrease in the rod responses, a square-shaped a-wave, an excessive increase in the b-wave in the bright flash responses, and decreased cone-derived responses. Mutational screening of the coding regions and flanking intronic sequences of the potassium channel, subfamily V, member 2 (KCNV2) gene was performed with bidirectional sequencing. The segregation of each allele was confirmed by screening other family members. Subsequent in silico analyses of the mutational consequences for protein function were performed. Results: There were two siblings from one family and one case in each of the two families. One family had a consanguineous marriage. Mutational screening revealed compound heterozygosity for the two alleles, p.C177R and p.G461R, in three patients, and homozygosity for complex alleles, p.R27H and p.R206P, in one patient from the consanguineous family. There were three putative novel variants, p.R27H, p.C177R, and p.R206P. The four variants in the families with KCNV2 were highly conserved in other species. In silico analyses predicted that all of the missense variants would alter protein function. Conclusions: Biallelic disease-causing variants were identified in four Japanese patients with CDSRR suggesting that the pathognomonic electrophysiological features are helpful in making a molecular diagnosis of KCNV2. Three novel variants were identified, and we conclude that there may be a distinct spectrum of KCNV2 alleles in the Japanese population.

Original languageEnglish
Pages (from-to)1580-1590
Number of pages11
JournalMolecular Vision
Volume19
Publication statusPublished - 2013 Jul 20

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Alleles
Computer Simulation
Potassium Channels
Marriage
Siblings
Proteins
Population
Genes

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Fujinami, K., Tsunoda, K., Nakamura, N., Kato, Y., Noda, T., Shinoda, K., ... Miyake, Y. (2013). Molecular characteristics of four Japanese cases with KCNV2 retinopathy: Report of novel disease-causing variants. Molecular Vision, 19, 1580-1590.

Molecular characteristics of four Japanese cases with KCNV2 retinopathy : Report of novel disease-causing variants. / Fujinami, Kaoru; Tsunoda, Kazushige; Nakamura, Natsuko; Kato, Yu; Noda, Toru; Shinoda, Kei; Tomita, Kaoru; Hatase, Tetsuhisa; Usui, Tomoaki; Akahori, Masakazu; Itabashi, Takeshi; Iwata, Takeshi; Ozawa, Yoko; Tsubota, Kazuo; Miyake, Yozo.

In: Molecular Vision, Vol. 19, 20.07.2013, p. 1580-1590.

Research output: Contribution to journalArticle

Fujinami, K, Tsunoda, K, Nakamura, N, Kato, Y, Noda, T, Shinoda, K, Tomita, K, Hatase, T, Usui, T, Akahori, M, Itabashi, T, Iwata, T, Ozawa, Y, Tsubota, K & Miyake, Y 2013, 'Molecular characteristics of four Japanese cases with KCNV2 retinopathy: Report of novel disease-causing variants', Molecular Vision, vol. 19, pp. 1580-1590.
Fujinami K, Tsunoda K, Nakamura N, Kato Y, Noda T, Shinoda K et al. Molecular characteristics of four Japanese cases with KCNV2 retinopathy: Report of novel disease-causing variants. Molecular Vision. 2013 Jul 20;19:1580-1590.
Fujinami, Kaoru ; Tsunoda, Kazushige ; Nakamura, Natsuko ; Kato, Yu ; Noda, Toru ; Shinoda, Kei ; Tomita, Kaoru ; Hatase, Tetsuhisa ; Usui, Tomoaki ; Akahori, Masakazu ; Itabashi, Takeshi ; Iwata, Takeshi ; Ozawa, Yoko ; Tsubota, Kazuo ; Miyake, Yozo. / Molecular characteristics of four Japanese cases with KCNV2 retinopathy : Report of novel disease-causing variants. In: Molecular Vision. 2013 ; Vol. 19. pp. 1580-1590.
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abstract = "Purpose: To describe the molecular characteristics of four Japanese patients with cone dystrophy with supernormal rod responses (CDSRR). Methods: Four individuals with a clinical and electrophysiological diagnosis of CDSRR were ascertained. The pathognomonic findings of the full-field electroretinograms (ERGs) included a decrease in the rod responses, a square-shaped a-wave, an excessive increase in the b-wave in the bright flash responses, and decreased cone-derived responses. Mutational screening of the coding regions and flanking intronic sequences of the potassium channel, subfamily V, member 2 (KCNV2) gene was performed with bidirectional sequencing. The segregation of each allele was confirmed by screening other family members. Subsequent in silico analyses of the mutational consequences for protein function were performed. Results: There were two siblings from one family and one case in each of the two families. One family had a consanguineous marriage. Mutational screening revealed compound heterozygosity for the two alleles, p.C177R and p.G461R, in three patients, and homozygosity for complex alleles, p.R27H and p.R206P, in one patient from the consanguineous family. There were three putative novel variants, p.R27H, p.C177R, and p.R206P. The four variants in the families with KCNV2 were highly conserved in other species. In silico analyses predicted that all of the missense variants would alter protein function. Conclusions: Biallelic disease-causing variants were identified in four Japanese patients with CDSRR suggesting that the pathognomonic electrophysiological features are helpful in making a molecular diagnosis of KCNV2. Three novel variants were identified, and we conclude that there may be a distinct spectrum of KCNV2 alleles in the Japanese population.",
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T2 - Report of novel disease-causing variants

AU - Fujinami, Kaoru

AU - Tsunoda, Kazushige

AU - Nakamura, Natsuko

AU - Kato, Yu

AU - Noda, Toru

AU - Shinoda, Kei

AU - Tomita, Kaoru

AU - Hatase, Tetsuhisa

AU - Usui, Tomoaki

AU - Akahori, Masakazu

AU - Itabashi, Takeshi

AU - Iwata, Takeshi

AU - Ozawa, Yoko

AU - Tsubota, Kazuo

AU - Miyake, Yozo

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N2 - Purpose: To describe the molecular characteristics of four Japanese patients with cone dystrophy with supernormal rod responses (CDSRR). Methods: Four individuals with a clinical and electrophysiological diagnosis of CDSRR were ascertained. The pathognomonic findings of the full-field electroretinograms (ERGs) included a decrease in the rod responses, a square-shaped a-wave, an excessive increase in the b-wave in the bright flash responses, and decreased cone-derived responses. Mutational screening of the coding regions and flanking intronic sequences of the potassium channel, subfamily V, member 2 (KCNV2) gene was performed with bidirectional sequencing. The segregation of each allele was confirmed by screening other family members. Subsequent in silico analyses of the mutational consequences for protein function were performed. Results: There were two siblings from one family and one case in each of the two families. One family had a consanguineous marriage. Mutational screening revealed compound heterozygosity for the two alleles, p.C177R and p.G461R, in three patients, and homozygosity for complex alleles, p.R27H and p.R206P, in one patient from the consanguineous family. There were three putative novel variants, p.R27H, p.C177R, and p.R206P. The four variants in the families with KCNV2 were highly conserved in other species. In silico analyses predicted that all of the missense variants would alter protein function. Conclusions: Biallelic disease-causing variants were identified in four Japanese patients with CDSRR suggesting that the pathognomonic electrophysiological features are helpful in making a molecular diagnosis of KCNV2. Three novel variants were identified, and we conclude that there may be a distinct spectrum of KCNV2 alleles in the Japanese population.

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