Achromatopsia is a congenital autosomal recessive disorder characterized by decreased or absent cone’s function. Clinical symptoms include photophobia, nystagmus, low best corrected visual acuity, complete or incomplete color vision. Mutations in the CNGA3 and CNGB3 genes are responsible for approximately 70–80 % of all achromatopsia cases. The purpose: to evaluate the results of a comprehensive clinical and genetic examinations of four patients with an established diagnosis of achromatopsia. Onset of the disease in all patients was in the form of severe photophobia and nystagmus, appearing at the age from 1.5 to 11 months. According to optical coherence tomography exams were detected structural changes in neuroepithelium (three patients), varied from subfoveal disorganization of the photoreceptor outer segments with “blurring” of the external limiting membrane line and ellipsoid zone to subfoveal destruction of the photoreceptor outer segments and the presence of a slit defect. Out of seven identified mutations in the CNGA3 and CNGB3 genes, two were previously detected in Russian patients, and five were not detected in the Russian Federation.

We present a clinical case of Norrie disease in a 6-year-old boy. The parents had in time an ophthalmologist consultation when the child was 4 months old, but the final diagnosis was made more than 5 years later. A specific feature of this case in addition to vitreoretinopathy and bilateral retinal detachment was the presence of a congenital malformation of the iris - aniridia, which is not a typical sign of Norrie disease. A modern method of genetic testing (next generation sequencing - NGS) made it possible to detect a previously undescribed mutation in the NDP gene and make a final clinical and genetic diagnosis. Key words: Norrie disease; vitreoretinopathy; retinal detachment; NDP gene.

The article presents recent worldwide achievements in the area of diagnosis and treatment of inherited retinal degenerations (IRDs) from the standpoint of ophthalmic genetics. Clinical studies conducted in patients with Leber congenital amaurosis and retinitis pigmentosa caused by biallelic mutations in the RPE65 gene have provided the basis for future genes studies associated with IRDs. The conducted studies highlight the importance of fundamental understanding of function of the gene, timely diagnosis and study of natural history of the disease. Currently, surgical techniques are being improved for the efficient delivery of gene preparations to target cells, as well as the criteria for evaluating treatment outcomes.

«Российская офтальмология онлайн» - электронное информационное издание, создается с 1 марта 2010 года под эгидой Российского общества офтальмологов. Основная задача проекта - научно-информационная поддержка специалистов в области офтальмологии.

This paper estimates the load and nosological spectrum of monogenic hereditary diseases (HDs) in Abazins of the Karachay-Cherkess Republic (KChR), identified in Cherkessk and ten districts, Abazinsky, Ust-Dzhegutinsky, Malokarachaevsky, Karachaevsky, Prikubansky, Khabezsky, Nogaysky, Adyge-Khablsky, Urupsky, and Zelenchuksky. The number of the investigated population was 387231 individuals (including 33264 Abazins). We detected 153 patients from 105 families with 45 nosological forms of HDs: 83 patients from 50 families with 23 AD diseases, 47 patients from 42 families with 15 AR diseases, and 23 patients from 13 families with 7 X-linked diseases. The total load of HDs in Abazins was 1:218 individuals (in the rural population 1:162, in the urban population 1:305). Frequent and rare nosological forms of HDs and the accumulation of certain diseases in Abazins in comparison with the previously surveyed populations of Russia were determined. On the basis of the prevalence of AD and AR hereditary diseases, a principal component analysis was carried out, which determined the genogeographical position of Abazins among nine ethnic groups (13 populations) of Russian Federation: six Russian regions, Bashkirs of the Bashkortostan, Tatars of the Tatarstan, Chuvashes of the Chuvashia, Maris of the Mari El, Udmurts of the Udmurtia, Adygeans of the Adygea, and Circassians and Abazins of the KChR.

The diversity and prevalence of hereditary diseases (HDs) among Nogais of the Karachay-Cherkess Republic (KChR) are described. The size of the surveyed KChR population was 387231 individuals, including 3.81% Nogais (14741 individuals). We revealed 36 nosological forms of HDs (110 patients from 81 families): 22 with autosomal dominant (AD) inheritance, 10 with autosomal recessive (AR) inheritance, and 4 with X-linked inheritance. The prevalence of HDs in Nogais was 1: 134. The features of HD diversity in Nogais were determined in comparison with the previously surveyed populations of Russia. The accumulation of Ehlers–Danlos syndrome (1: 388), AD amelogenesis imperfecta (1: 3685), AD ichthyosis (1: 4914), AR nonsyndromic mental retardation (1: 1340), AR Gilbert syndrome (1: 4914), and X-linked inherited deficit of glucose-6-dehydrogenase (1: 1774 males) was established. The analysis of heterozygous carriage of mutations “major” for Russia in the genes of the four following AR diseases in 118 unrelated clinically healthy Nogais (236 analyzed chromosomes) was performed: cystic fibrosis (13 mutations in the CFTR gene: CFTRdele2,3 (21 kb), F508del, I507del, 1677delTA, 2184insA, 2143delT, 2183AA>G, 2184delA, 394delTT, 3821delT, L138ins, E92K, W1282X); phenylketonuria (six frequent mutations in the PAH gene: R261X, R408W, R413P, F331S, P211T, P211L); nonsyndromic sensorineural hearing loss (35delG mutation in the GJB2 gene); and Gilbert syndrome (an increase in the number of TA repeats in the UGT1A1 gene). Allelic specificity for all studied genes in the Nogai people was revealed.

Purpose. To evaluate the results in genetic consulting of patients with various forms of congenital and hereditary eyes pathology.Material and methods. The study is based on an analysis of results in genetic consulting and molecular genetic investigations of DNA samples of 18 patients: congenital corneal dystrophy (n=3); congenital cataract (n=11); Norrie disease (n = 4). All patients had a comprehensive ophthalmologic clinical and functional examination according to the forms of pathology. Geneticist physician conducted a genealogical analysis. A study of exons and flanking intronic regions was performed using methods of analysis of amplified fragment length polymorphism, restriction fragments and direct sequencing.Results. The clinical diagnosis of endothelial corneal dystrophy with autosomal recessive mode of inheritance using molecular genetic methods in 2 of the 3 cases was confirmed, and a de novo mutation in the gene SLC4A11 non-described previously was found. In the group with hereditary diseases the lens pathogenic mutations were detected in the GJA3 andGJA8 genes in 2 of 11 cases (18%). Pathogenic mutations in NDP gene were detected only in 2 of 4 family members studied, and its sibling proband, directed to the genetic analysis of patients with a clinical diagnosis Norrie disease. In another of the studied probands the diseasecausing mutation was not reveled, and thus, the molecular genetic diagnosis of Norrie disease was not confirmed.Conclusion. For the first time in the Russian Federation pathogenic mutations in the gene SLC4A11 collagen, previously did not described in the literature, were revealed in patients with congenital endothelial corneal dystrophy, in a patient with congenital cataract in the gene GJA8. The success of genetic consulting depends on the complete genealogical analysis, and the correct determination of the clinical and genetic form of pathology.

Purpose. Retrospective genetic counseling analysis of patients with hereditary retinal diseases.Material and methods. The study is based on an analysis of genetic counseling and molecular genetic studies of DNA samples of 82 patients: Stargardt disease (n=37), Fundus Flavimaculatus (n=34), Best vitelliform macular dystrophy (n=11). All patients had a comprehensive ophthalmologic clinical and functional examination. Geneticist physician conducted a genealogical analysis. Search for mutations at each clinical form of the disease was carried out after a verification of clinical and genetic disease forms. The exons and flanking intronic regions were studied using methods of analysis of amplified fragment length polymorphism, restriction fragments and direct sequencing. Results. The searched pathogenic mutations were identified in pro-bands in 46% of cases in patients with a clinical diagnosis of Stargardt disease and in both of family members aimed at analyzing. Mutations were not detected in the ELOVL4 gene. One or more pathogenic mutations in probands with Fundus Flavimaculatus were revealed in 46% of cases. Diagnosis of Best vitelliform macular dystrophy was molecular genetically confirmed in 8 patients. The results of genetic counseling of patients with hereditary diseases of the retina, as well as members of their families showed a clinical and genetic diversity and difficulties in the diagnosis of this group of diseases in Russia.Conclusion. Complex clinical, functional and molecular genetic testing all members of proband’s family allows to increase the rate of detection in carriers of pathogenic mutations without any clinical appearance of the disease. Identification of the most frequent mutations in different genetic ophthalmic pathology in patients of the Russian Federation allows to create the «DNA panel» for genetic studies, which increase an availability of such studies for the population, as well as lead to a speedy implementation of screening methods of DNA diagnosis i n the practical healthcare.

Starghardt macular dystrophy is one of the most common hereditary macular dystrophies. ABCR gene has a high level of polymorphism, multiple pathological mutations and difficult feature of inheritance. All these factors determine the special methods of clinical and molecular genetic diagnosis.

The present study involved 48 patients at the age varying from 7 to 52 years referred to our clinic with the diagnosis of central retinal Stargardt’s dystrophy. The combined application of clinical methods and functional tests including visiometry, dynamic and static perimetry, assessment of colourperception, electroretinography, optical coherence tomography, fundus photography, biomicroscopy, direct and indirect ophthalmoscopy, fluorescence angiography, autofluorescence imaging, and molecular genetic studies made possible clinical verification of central retinal Stargardt’s dystrophy that gave evidence of the high percentage of errors in the primary diagnosis. It is concluded that the proposed integrated approach permits to develop the criteria for early differential diagnostics of central retinal Stargardt’s dystrophy.

Disease Shtargardt is one of the most common hereditary central macular dystrophy and up to 7% of all retinal dystrophies. Despite the well-described in the literature clinical and ophthalmoscopic criteria Shtargardt`s disease and other hereditary retinal dystrophies, often one and the same disease described by different doctors with different names or, alternatively, combined into a single concept of a very distant form. The authors examined 32 patients (64 eyes) with presumed diagnosis of the disease Shtargardt. In the differential diagnosis of the diagnosis was confirmed in 31.3% of cases.