Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti | 2019
Molecular genetic cause of achromatopsia in two patients of Czech origin.
Abstract
INTRODUCTION\nAchromatopsia is an autosomal recessive retinal disorder with an estimated prevalence ranging from 1 in 30.000 to 50.000. The disease is caused by mutations in six different genes. The aim of the study was to perform molecular genetic analysis in 11 unrelated probands with a\xa0clinical diagnosis of achromatopsia and to describe clinical findings in those that were found to carry biallelic pathogenic mutations.\n\n\nMETHODS\nAll probands and their parents underwent ophthalmic examination. Mutation detection was performed using Sanger sequencing of CNGB3 exons 6, 7, 9-13, which have been found to harbour most disease-causing mutations in patients with achromatopsia of European origin.\n\n\nRESULTS\nThree known pathogenic variants in CNGB3 were identified in 2 probands. Proband 1 was a\xa0compound heterozygote for the c.819_826del; p.(Arg274Valfs*13) and c.1006G>T; p.(Glu336*). Proband 2 carried the c.1148del; p.(Thr383Ilefs*13) in a\xa0homozygous state. The best corrected visual acuity in proband 1 (aged 19 years) was 0.1 in both eyes, in proband 2 (aged 8 years) 0.05 in the right eye and 0.1 in the left eye. Both individuals had nystagmus, photophobia, and absence of colour discrimination. Fundus examination appeared normal however spectral-domain optical coherence tomography revealed subtle bilaterally symmetrical structural changes in the fovea.\n\n\nCONCLUSION\nMolecular genetic analysis of Czech patients with achromatopsia was performed for the first time. Identification of disease-causing mutations in achromatopsia is important for establishing an early diagnosis, participation in clinical trials assessing gene therapies and may be also used for preimplantation genetic diagnosis.