Abstract
Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
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Acknowledgements
We thank all patients and family members for participating in this study, and Manfred Stuhrmann-Spangenberg, Jennifer Kemp, Karmen Trzupek, and Gert Matthijs for supplying us with patients and blood/DNA samples. We also thank Jochen Scholl, Martina Borghammer, Sabine Tippmann, and Eva Weber for excellent technical assistance. This work was supported by the following grants: Grant IB2 and Q1 from the Bundesministerium für Bildung und Forschung (01 KS 9602) and the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Tübingen to LTS and BW; a grant of the Schilling Stiftung to LTS; Grants SFB430/A5 and W: 1189/6-1 of the Deutsche Forschungsgemeinschaft to BW; Grant 32-065250.01 from the Swiss National Science Foundation to FLM; Grant DFGLo457,1–3 of the Deutsche Forschungsgemeinschaft to BL; a grant from the Foundation Fighting Blindness and Research to Prevent Blindness to RGW. CR: None.
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Kohl, S., Varsanyi, B., Antunes, G. et al. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet 13, 302–308 (2005). https://doi.org/10.1038/sj.ejhg.5201269
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DOI: https://doi.org/10.1038/sj.ejhg.5201269
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