CNGA3 Mutations in Hereditary Cone Photoreceptor Disorders
| Autor: | Daphne Gamer, Samuel G. Jacobson, Martina Broghammer, Roberto Giorda, Roberto Salati, Ulrich Kellner, Carel B. Hoyng, Sinan Tatlipinar, Susanne Kohl, Thomas Rosenberg, Pierre Bitoun, Gerhard Wolff, Herbert Jägle, Bernd Wissinger, E. Cumhur Sener, Eberhart Zrenner, Günter Rudolph, Sabine Tippmann, Frans P.M. Cremers, Marianne Schwartz, Tim Marx, Bernhard Jurklies, Eckart Apfelstedt-Sylla, Claudio Castellan, Christine Verellen-Dumoulin, Simone Mayer, Birgit Lorenz, Sten Andréasson, Lindsay T. Sharpe |
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| Přispěvatelé: | Göz Hastalıkları |
| Rok vydání: | 2001 |
| Předmět: |
Achromatopsia
Protein Conformation Elucidation of hereditary disorders and their molecular diagnosis Mutant DNA Mutational Analysis Molecular Sequence Data Mutation Missense Cyclic Nucleotide-Gated Cation Channels Biology Ion Channels Conserved sequence Evolution Molecular Gene Frequency medicine Genetics Missense mutation Animals Humans Genetics(clinical) Amino Acid Sequence experimenteel en klinisch onderzoek en behandeling. [Erfelijke en verworven vitreo-retinale aandoeningen] Allele Gene Genetics (clinical) Conserved Sequence Genetics & Heredity GNAT2 Polymorphism Genetic Base Sequence Haplotype Eye Diseases Hereditary Exons Articles medicine.disease Introns Phenotype Haplotypes Mutation Disease Progression Retinal Cone Photoreceptor Cells experimental and clinical research and treatment. [Hereditary and acquired vitreo-retinal disorders] Opheldering van erfelijke ziekten en hun moleculaire diagnostiek |
| Zdroj: | American Journal of Human Genetics, 69, 4, pp. 722-737 American Journal of Human Genetics, 69, 722-737 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/323613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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