Journalartikel
Autorenliste: Solaki, Maria; Baumann, Britta; Reuter, Peggy; Andreasson, Sten; Audo, Isabelle; Ayuso, Carmen; Balousha, Ghassan; Benedicenti, Francesco; Birch, David; Bitoun, Pierre; Blain, Delphine; Bocquet, Beatrice; Branham, Kari; Catala-Mora, Jaume; De Baere, Elfride; Dollfus, Helene; Falana, Mohammed; Giorda, Roberto; Golovleva, Irina; Gottlob, Irene; Heckenlively, John R.; Jacobson, Samuel G.; Jones, Kaylie; Jaegle, Herbert; Janecke, Andreas R.; Kellner, Ulrich; Liskova, Petra; Lorenz, Birgit; Martorell-Sampol, Loreto; Messias, Andre; Meunier, Isabelle; Belga Ottoni Porto, Fernanda; Papageorgiou, Eleni; Plomp, Astrid S.; de Ravel, Thomy J. L.; Reiff, Charlotte M.; Renner, Agnes B.; Rosenberg, Thomas; Rudolph, Guenther; Salati, Roberto; Sener, E. Cumhur; Sieving, Paul A.; Stanzial, Franco; Traboulsi, Elias, I; Tsang, Stephen H.; Varsanyi, Balazs; Weleber, Richard G.; Zobor, Ditta; Stingl, Katarina; Wissinger, Bernd; Kohl, Susanne
Jahr der Veröffentlichung: 2022
Seiten: 832-858
Zeitschrift: Human Mutation: Variation, Informatics and Disease
Bandnummer: 43
Heftnummer: 7
ISSN: 1059-7794
eISSN: 1098-1004
DOI Link: https://doi.org/10.1002/humu.24371
Verlag: Wiley
Abstract:
Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying "likely disease-causing" variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as "likely disease-causing" according to ACMG/AMP criteria. We report 48 novel "likely disease-causing" variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.
Zitierstile
Harvard-Zitierstil: Solaki, M., Baumann, B., Reuter, P., Andreasson, S., Audo, I., Ayuso, C., et al. (2022) Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia, Human Mutation: Variation, Informatics and Disease, 43(7), pp. 832-858. https://doi.org/10.1002/humu.24371
APA-Zitierstil: Solaki, M., Baumann, B., Reuter, P., Andreasson, S., Audo, I., Ayuso, C., Balousha, G., Benedicenti, F., Birch, D., Bitoun, P., Blain, D., Bocquet, B., Branham, K., Catala-Mora, J., De Baere, E., Dollfus, H., Falana, M., Giorda, R., Golovleva, I., ...Kohl, S. (2022). Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia. Human Mutation: Variation, Informatics and Disease. 43(7), 832-858. https://doi.org/10.1002/humu.24371
Schlagwörter
achromatopsia; ALPHA-SUBUNIT; CNGA3; cyclic nucleotide-gated ion channel; FUNCTIONAL-ANALYSIS; in silico analysis; JAPANESE PATIENT; MOLECULAR-GENETICS; NONSENSE MUTATION; NUCLEOTIDE-GATED CHANNELS; PAKISTANI FAMILIES; PHOTORECEPTOR DEGENERATION; TOTAL COLOURBLINDNESS; variant classification; variant spectrum
