Epidemiologic, clinical and pathogenesis features of achromatopsia in the Russian population

Achromatopsia (ACHM) is a rare autosomal recessive disease. Its mutation spectrum is well described in other populations, but the data on ACHM prevalence and features in Russia are insufficient. Purpose. To describe clinically and genetically the Russian cohort of AHCM for the potential use of targeted treatment approaches, including gene therapy. Material and methods. Out of 18 patients with clinical manifestations of ACHM, 10 patients were chosen (6 with no kinship relatedness and 4 with kinship relatedness) aged 12.3 ± 5.8 years. These patients underwent standard ophthalmologic examination: visometry, perimetry, biomicroscopy, ophthalmoscopy, as well as optical coherence tomography, electroretinography, and color test on distinguishing color shades, in order to determine the clinical characteristics of ACHM. Molecular genetic confirmation of the clinical diagnosis was performed by high-performance parallel DNA sequencing. An in silico analysis of pathogenetic pathways of the clinical picture in 10 patients with confirmed ACHM was performed. Results. In the examined Russian patients, previously determined mutations in the CNGA3 and CNGB3 genes were confirmed. The most common mutation was a single nucleotide deletion with a reading frame shift in the 10th exon of the CNGB3 gene; a missense mutation in the 8th exon of the CNGA3 gene was second frequent. One patient had mutations in the CNGA3 and CNGB3 genes. Segregation analysis confirms the autosomal recessive nature of disease inheritance. Mutations in the CNGB3 gene have been observed to lead to more serious clinical manifestations than mutations in CNGA3. Conclusions. The analysis of the Russian ACHM cohort shows that mutations in the CNGA3 and CNGB3 genes are the main cause of the development of the disease. A complete molecular genetic confirmation of the clinical diagnosis has been obtained, which is necessary for prescribing targeted treatment to patients, including gene therapy.

achromatopsia, ACHM, genes CNGA3, CNGB3, Russian cohort

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