TY - JOUR
T1 - CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
AU - Kohl, Susanne
AU - Varsanyi, Balazs
AU - Antunes, Gesine Abadin
AU - Baumann, Britta
AU - Hoyng, Carel B.
AU - Jägle, Herbert
AU - Rosenberg, Thomas
AU - Kellner, Ulrich
AU - Lorenz, Birgit
AU - Salati, Roberto
AU - Jurklies, Bernhard
AU - Farkas, Agnes
AU - Andreasson, Sten
AU - Weleber, Richard G.
AU - Jacobson, Samuel G.
AU - Rudolph, Günther
AU - Castellan, Claudio
AU - Dollfus, Helene
AU - Legius, Eric
AU - Anastasi, Mario
AU - Bitoun, Pierre
AU - Lev, Dorit
AU - Sieving, Paul A.
AU - Munier, Francis L.
AU - Zrenner, Eberhart
AU - Sharpe, Lindsay T.
AU - Cremers, Frans P.M.
AU - Wissinger, Bernd
N1 - Funding Information:
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.
PY - 2005/3
Y1 - 2005/3
N2 - 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 1bp 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.
AB - 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 1bp 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.
KW - ACHM3 locus
KW - Achromatopsia
KW - CNGB3 mutations
KW - Cyclic nucleotide-gated channel
KW - Rod monochromacy
KW - Total colorblindness
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U2 - 10.1038/sj.ejhg.5201269
DO - 10.1038/sj.ejhg.5201269
M3 - Article
C2 - 15657609
AN - SCOPUS:20144382218
SN - 1018-4813
VL - 13
SP - 302
EP - 308
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 3
ER -