Clinical and genetic features of Hungarian achromatopsia patients.
OBJECTIVE
To describe the clinical features and molecular genetic findings in a collection of Hungarian achromatopsia patients.


METHODS
Twelve patients with congenital achromatopsia from nine Hungarian families were analyzed in this study. The patients underwent standard ophthalmological examination including detailed full-field electroretinography and color vision testing. In two patients, dark adaptation and spectral luminosity tests were also performed. PCR/RFLP analysis and DNA sequencing was applied for mutation screening of CNGA3 and CNGB3. Heterologous minigene expression was used to evaluate transcript splicing of a new intronic mutation in CNGB3.


RESULTS
Mutations in CNGA3 were present in four families and mutations in CNGB3 in the remaining five families, including mutations known from Western European patient samples and two new CNGB3 mutations: c.112C>T/Gln38X and c.1663-5T>G. Heterologous expression in COS7 cells shows that the latter induces a splicing defect through the activation of a cryptic splice site 4 bases upstream of the genuine splice site. The patients presented with a clinical picture typical for congenital achromatopsia and there was no significant difference in the phenotype of subjects with either CNGA3 or CNGB3 mutations based on standard ophthalmological examination. However, we assume residual cone function in a subject homozygous for the Phe547Leu mutation in CNGA3 based on prior detailed psychophysical testing (i.e., dark adaptation and spectral luminosity).


CONCLUSIONS
Mutations in CNGA3 and CNGB3 account for achromatopsia in Hungarian patients including known mutations and a few new CNGB3 mutations. While standard ophthalmological examination revealed a phenotype of complete achromatopsia, we show that thorough psychophysical testing can help to identify subjects with some minute cone function.
Varsányi
Balázs
B
Molecular Genetics Laboratory, University Eye Hospital, University of Tübingen, Tübingen, Germany. varsika@axelero.hu
Wissinger
Bernd
B
Kohl
Susanne
S
Koeppen
Katja
K
Farkas
Agnes
A
D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D003119:Color Perception Tests; D003117:Color Vision Defects / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology*; D054815:Cyclic Nucleotide-Gated Cation Channels; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D012326:RNA Splicing / Q000235:genetics; D012160:Retina / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels