Clinical and genetic features of Hungarian achromatopsiapatients

[摘要] Purpose: To describe the clinical features and molecular geneticfindings in a collection of Hungarian achromatopsia patients.Methods: Twelve patients with congenital achromatopsia from nineHungarian families were analyzed in this study. The patients underwentstandard ophthalmological examination including detailed full-fieldelectroretinography and color vision testing. In two patients, darkadaptation and spectral luminosity tests were also performed. PCR/RFLPanalysis and DNA sequencing was applied for mutation screening of CNGA3and CNGB3. Heterologous minigene expression was used to evaluatetranscript splicing of a new intronic mutation in CNGB3.Results: Mutations in CNGA3 were present in four families andmutations in CNGB3 in the remaining five families, including mutationsknown from Western European patient samples and two new CNGB3 mutations:c.112C>T/Gln38X and c.1663-5T>G. Heterologous expression in COS7cells shows that the latter induces a splicing defect through theactivation of a cryptic splice site 4 bases upstream of the genuinesplice site. The patients presented with a clinical picture typical forcongenital achromatopsia and there was no significant difference in thephenotype of subjects with either CNGA3 or CNGB3 mutations based onstandard ophthalmological examination. However, we assume residual conefunction in a subject homozygous for the Phe547Leu mutation in CNGA3based on prior detailed psychophysical testing (i.e., dark adaptationand spectral luminosity).Conclusions: Mutations in CNGA3 and CNGB3 account for achromatopsiain Hungarian patients including known mutations and a few new CNGB3mutations. While standard ophthalmological examination revealed aphenotype of complete achromatopsia, we show that thoroughpsychophysical testing can help to identify subjects with some minutecone function.

[学科分类] 生物化学/生物物理