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Susanne Kohl, Tanja Grau, Simone Schaich, Britta Baumann, Bernd Wissinger; Disease Gene Prevalences And Mutation Spectra In Autosomal Recessive Achromatopsia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5382.
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© ARVO (1962-2015); The Authors (2016-present)
Achromatopsia (syn.: rod monochromatism, total colorblindness) is a rare autosomal recessive inherited retinal disorder characterized by the absence of color discrimination, low visual acuity, photophobia and congenital nystagmus. Here we provide valid and reliable data on the genetic basis of achromatopsia in the Caucasian population including the prevalence of the known disease genes (CNGA3, CNGB3, GNAT2 and PDE6C) and the diversity and frequencies of mutations in these genes.
All coding exons and flanking intron sequences of CNGA3, CNGB3, GNAT2 and PDE6C were continuously screened in over 600 independent clinically diagnosed achromatopsia patients by means of PCR amplification from genomic DNA and direct Sanger sequencing. Segregation analysis was carried out where DNA samples from family members were available.
We were able to identify mutations in 579 patient from 397 individual families with a clinical diagnosis of autosomal recessive achromatopsia: 216 patients (141 families) carried mutations in CNGA3, 336 patients (237 families) in CNGB3, 16 patients (12 families) carried mutations in GNAT2, and 11 patients (7 families) in PDE6C. Single heterozygous mutations were observed in 6 cases in CNGA3 and in 27 patients in CNGB3. The complete mutation spectra comprised <100 different mutations in CNGA3, 58 mutations in CNGB3, 14 mutations in GNAT2 and 11 mutations in PDE6C.
CNGB3/ACHM3 remains the major locus for achromatopsia accounting for ~40% of all affected patients, while mutations in CNGA3/ACHM2 are responsible for ~30% of achromats in our patient sample. In contrast, GNAT2/ACHM4 and PDE6C/ACHM5 only play a minor role with 2% and 1.5% of patients carrying mutations in these genes, respectively. Our data and patient sample will be valuable to support clinical and therapeutic studies on achromatopsia, which is currently being considered as a major target for retinal gene therapy.
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