Journalartikel
Autorenliste: Wissinger, Bernd; Schaich, Simone; Baumann, Britta; Bonin, Michael; Jaegle, Herbert; Friedburg, Christoph; Varsanyi, Balazs; Hoyng, Carel B.; Dollfus, Helene; Heckenliyely, John R.; Rosenberg, Thomas; Rudolph, Guenter; Kellner, Ulrich; Salati, Roberto; Plomp, Astrid; De Baere, Elfride; Andrassi-Darida, Monika; Sauer, Alexandra; Wolf, Christiane; Zobor, Ditta; Bernd, Antje; Leroy, Bart P.; Enyedi, Peter; Cremers, Frans P. M.; Lorenz, Birgit; Zrenner, Eberhart; Kohl, Susanne
Jahr der Veröffentlichung: 2011
Seiten: 1398-1406
Zeitschrift: Human Mutation: Variation, Informatics and Disease
Bandnummer: 32
Heftnummer: 12
ISSN: 1059-7794
Open Access Status: Green
DOI Link: https://doi.org/10.1002/humu.21580
Verlag: Wiley
Abstract:
Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very rare autosomal recessive retinal disorder. CDSRR is associated with mutations in KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage-gated potassium channel. In this study, we found that KCNV2 mutations are present in a substantial fraction (2.24.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR is underdiagnosed and more common than previously thought. In total, we identified 20 different KCNV2 mutations; 15 of them are novel. A new finding of this study is the substantial proportion of large deletions at the KCNV2 locus that accounts for 15.5% of the mutant alleles in our sample. We determined the breakpoints and size of all five different deletions, which ranged between 10.9 and 236.8 kb. Two deletions encompass the entire KCNV2 gene and one also includes the adjacent VLDLR gene. Furthermore, we investigated N-terminal amino acid substitution mutations for its effect on interaction with Kv2.1 using yeast two-hybrid technology. We found that these mutations dramatically reduce or abolish this interaction suggesting a lack of assembly of heteromeric Kv channels as one underlying pathomechanism of CDSRR. 32:13981406, 2011. (C) 2011 Wiley Periodicals, Inc.
Zitierstile
Harvard-Zitierstil: Wissinger, B., Schaich, S., Baumann, B., Bonin, M., Jaegle, H., Friedburg, C., et al. (2011) Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response, Human Mutation: Variation, Informatics and Disease, 32(12), pp. 1398-1406. https://doi.org/10.1002/humu.21580
APA-Zitierstil: Wissinger, B., Schaich, S., Baumann, B., Bonin, M., Jaegle, H., Friedburg, C., Varsanyi, B., Hoyng, C., Dollfus, H., Heckenliyely, J., Rosenberg, T., Rudolph, G., Kellner, U., Salati, R., Plomp, A., De Baere, E., Andrassi-Darida, M., Sauer, A., Wolf, C., ...Kohl, S. (2011). Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response. Human Mutation: Variation, Informatics and Disease. 32(12), 1398-1406. https://doi.org/10.1002/humu.21580
Schlagwörter
ALPHA-SUBUNITS; CEREBELLAR HYPOPLASIA; CHANNEL; ELECTRORETINOGRAM; KCNV2; Kv channel; LIPOPROTEIN RECEPTOR GENE; QUADRUPEDAL LOCOMOTION; retinal dystrophy
