Wissinger, Bernd and Gamer, Daphne and Jaegle, Herbert and Giorda, Roberto and Marx, Tim and Mayer, Simone and Tippmann, Sabine and Broghammer, Martina and Jurklies, Bernhard and Rosenberg, Thomas and Jacobson, Samuel G. and Sener, E. Cumhur and Tatlipinar, Sinan and Hoyng, Carel B. and Castellan, Claudio and Bitoun, Pierre and Andreasson, Sten and Rudolph, Günter and Kellner, Ulrich and Lorenz, Birgit and Wolff, Gerhard and Verellen-Dumoulin, Christine and Schwartz, Marianne and Cremers, Frans P. M. and Apfelstedt-Sylla, Eckart and Zrenner, Eberhart and Salati, Roberto and Sharpe, Lindsay T. and Kohl, Susanne (2001) CNGA3 mutations in hereditary cone photoreceptor disorders. AMERICAN JOURNAL OF HUMAN GENETICS, 69 (4). pp. 722-737. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
We recently showed that mutations in the CNGA3 gene encoding the alpha -subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CGMP-GATED CHANNEL; ALPHA-SUBUNIT; TOTAL COLOURBLINDNESS; COLOR-VISION; ACHROMATOPSIA; GENE; PINGELAPESE; LOCUS; EYE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Ophthalmologie, Strabismologie und Ophthalmogenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Dec 2021 07:36 |
| Last Modified: | 06 Dec 2021 07:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/41045 |
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