Abstract
Abstract: :
Purpose: Achromatopsia (syn.: Rodmonochromacy, Total Colorblindness) is an autosomal recessively inherited disorder characterized by the absence of color discrimination, low visual acuity, photophobia and congenital nystagmus. Mutations in the CNGA3 gene on chromosome 2q11 (ACHM2) and the CNGB3 gene on chromosome 8q21 (ACHM3), which encode the alpha– and the beta–subunits of the cyclic nucleotide gated cation channel (CNG) in cone photoreceptors, respectively, but also in the GNAT2 gene on chromosome 1p13 (ACHM4), encoding the alpha–subunit of the cone photoreceptor transducin, have been shown to cause this disorder. All three gene products are involved in the cone phototransduction cascade. Methods: We have screened the CNGA3, the CNGB3 and the GNAT2 gene in over 400 independent patients diagnosed with complete or incomplete achromatopsia by means of PCR amplification of all coding exons with primers derived from adjacent intronic sequences followed by direct sequencing, PCR/RFLP or SSCP assays. Results: Here we report the results of the mutation screening of the CNGA3, the CNGB3 and the GNAT2 genes in families with patients affected by achromatopsia. The mutation spectra comprise 67 different mutations in CNGA3, 30 in CNGB3 and 7 in GNAT2. In all, we were able to identify both mutant alleles in our patient sample as follows: 94 independent patients carried mutations in CNGA3 and 169 patients in CNGB3; only 5 patients carried mutations in GNAT2. Single CNGA3 mutations were observed in 4 cases and single CNGB3 mutations in 16 patients. We also report the frequency of different recurrent mutations, like the c.1148delC allele in CNGB3 which accounts for over 70% of all CNGB3 mutant alleles. Conclusions: Our data show that mutations in all three genes result in complete achromatopsia with indistinguishable phenotypes. Yet few cases with incomplete achromatopsia and mutations in the CNGA3 or the GNAT2 gene have been observed. CNGB3/ACHM3 is the major locus for achromatopsia accounting for 40–50% of all affected patients. CNGA3/ACHM2 is responsible for 20–30% of all achromats, while GNAT2/ACHM4 plays a minor role in this disorder with less than 2%.
Keywords: mutations • color vision • retina