Study of the hereditary non-syndromic ophthalmological pathology of child population of the Karachay-Cherkess Republic: estimations of genetic load and molecular genetic analysis

V.V. Kadyshev1, A.V. Marakhonov1, S.I. Kutsev1,2, R.A. Zinchenko1,3 1 Research Centre of Medical Genetics of the Russian Academy of Medical Sciences, Moscow,&nbsp;Russian Federation 2 Pirogov Russian National Research Medical University, Moscow, Russian Federation 3 M. F. Vladimirsky Moscow Regional Research and Clinical Institute (MONIKI), Moscow,&nbsp;Russian Federation Abstract The publication continues the previously presented data on the study of the epidemiology of ophthalmic diseases in the children of the Karachay-Cherkess Republic. Genetic epidemiological study of the population includes the study of a wide range of aspects. The structure of the nosological spectrum was published previously. The study of the genetic load is an integral part of this work. Aim: the purpose of this study was to investigate the specific features of the genetic load of hereditary non-syndromic ophthalmologic pathology in the population of the Karachay-Cherkess Republic. Patients and Methods: 90 793 children from 10 districts of the Karachay-Cherkess Republic aged 0–18 were examined, of which 121 were included in the sample. The biomaterial (peripheral venous blood) is taken from a part of patients taking into account the legislative and legal standards of the Russian Federation. In the study, genetic-epidemiological, statistical, molecular-genetic methods of examination were used. Results: the values of genetic load of non-syndromic hereditary eye pathology in the child population of 10 districts of the Karachay-Cherkess Republic and the city of Cherkessk is established. The total load of the non-syndromic hereditary pathology of the eye was 1.33±0.12. Statistical analysis of the obtained genetic load data demonstrated significant differences between autosomal dominant pathology in rural and urban populations (for rural population — t=2.3, for urban — t=2.8). The group of patients underwent confirmatory molecular genetic diagnosis. Conclusions: 1. The genetic load of the hereditary pathology of the organ of vision in the Karachay-Cherkess Republic among children was 1.33±0.12. 2. The prevalence of AD pathology over diseases with AR inheritance in both rural and urban subpopulations was revealed. 3. Region-specific molecular genetic markers for the hereditary pathology of the organ of vision are not established at this stage. Key words: epidemiology, genetics, genetic load, DNA diagnosis, children, Karachay-Cherkess Republic. For citation: Kadyshev V.V., Marakhonov A.V., Kutsev S.I., Zinchenko R.A. Study of the hereditary non-syndromic ophthalmological pathology of child population of the Karachay-Cherkess Republic: estimations of genetic load and molecular genetic analysis.&nbsp;RMJ “Clinical ophthalmology”. 2018;3:134–139. <br

Complex treatment approach to primary open-angle glaucoma: focus on neuroprotection

M.&nbsp;Kh. Khubetsova1, V.V. Kadyshev2, B.F. Ambalova3 1S.N. Fedorov NMRC “MNTK “Eye Microsurgery”, Moscow, Russian Federation 2Moscow Genetic Research Center, Moscow, Russian Federation 3Right-Shore Central Regional Clinical Hospital, Beslan, Russian Federation According to the WHO, glaucoma is now the second leading cause of blindness globally. It was demonstrated that effective treatment for glaucoma should include both IOP reduction and neuroprotection. However, even pathogenic treatment for glaucoma can be ineffective due to the poor adherence to treatment. Currently, treatment compliance is of great importance. Ocular surface disorders inevitably resulting from long-term instillations of IOP-lowering medications are among the factors affecting medication non-adherence. Tear replacement therapy is a potential solution which, however, increases the number of medications and instillations and results in poor medication adherence. Brimonidine tartrate 0.2% provides both IOP-lowering and neuroprotective effects while polyvinyl alcohol moisturize and protects ocular surface. Polyvinyl alcohol improves dry eye symptoms in long-term therapy when adding brimonidine to glaucoma treatment. Keywords: glaucoma, intraocular pressure, neuroprotection, ocular surface, compliance, brimonidine, Luxfen. For citation: Khubetsova M.Kh., Kadyshev V.V., Ambalova B.F. Complex treatment approach to primary open-angle glaucoma: focus on neuroprotection. Russian Journal of Clinical Ophthalmology. 2019;19(4):224–228. <br

Study of hereditary non-syndromic ophthalmic pathology of child population of the Karachay-Cherkess Republic: features and structure of nosological spectrum

V.V. Kadyshev1, A.V. Marakhonov1, S.I. Kutsev1,2, R.A. Zinchenko1,3 1 Research Centre of Medical Genetics of the Russian Academy of Medical Sciences, Moscow, &nbsp;Russian Federation 2 Pirogov Russian National Research Medical University, Moscow, Russian Federation 3 M.F. Vladimirsky Moscow Regional Research and Clinical Institute (MONIKI), Moscow,&nbsp; &nbsp;Russian Federation The publication is a continuation of the previously submitted data on the study of the epidemiology of ophthalmic diseases in children of the Karachay-Cherkess Republic. Genetic and epidemiological study of the population includes a research of a wide range of indicators. A burden assessment of the hereditary ocular pathology of the child population of the surveyed region and the data of molecular genetic diagnostics were published earlier. This article presents structure and features of a nosological spectrum of the visual organ hereditary pathology. Aim: to study the nosological spectrum and its features of hereditary non-syndromic ophthalmic pathology among the child population of the Karachay-Cherkess Republic. Patients and Methods: 90793 children from 10 regions of the Karachay-Cherkess Republic between the ages of 0 and 18 were examined, of which 121 people were enrolled in set. To solve the problem, genetic and epidemiological, clinical, paraclinical examination methods were used. Results: the structure and features of the nosological spectrum of non-syndromic hereditary ophthalmic pathology were determined in the child population of 10 regions of the Karachay-Cherkess Republic and the city of Cherkessk. Congenital malformations of the visual organ and hereditary pathology of the posterior segment of an eye (58%) make the main contribution to the prevalence. An overall prevalence of hereditary ocular pathology was at ratio 1:671. It was revealed that a large proportion of hereditary diseases of the visual organ with an autosomal dominant inheritance pattern (1:1163). The prevalence of autosomal recessive pathology was at ratio 1:2268 of people. Conclusion: autosomal dominant diseases make a greater contribution to the structure of the nosological spectrum — 1:1163. Congenital malformations of the visual organ and pathology of the posterior segment of the eye are prevalent in the structure of the pediatric nosological spectrum. Key words: epidemiology, genetics, hereditary pathology, nosological spectrum, children, Karachay-Cherkess Republic. For citation: Kadyshev V.V., Marakhonov A.V., Kutsev S.I., Zinchenko R.A. Study of hereditary non-syndromic ophthalmic pathology of child population of the Karachay-Cherkess Republic: features and structure of nosological spectrum. Russian Journal of Clinical Ophthalmology. 2019;19(1):7–12. About the authors:&nbsp; 1Vitalii V. Kadyshev — MD, PhD, Senior Researcher of the Laboratory of Genetic Epidemiology;&nbsp; 1Andrei V. Marakhonov — PhD, Biology, Senior Researcher of the Laboratory of Genetic Epidemiology;&nbsp; 1,2&nbsp;Sergei I. Kutsev — MD, PhD, Professor, Сorresponding Member of RAS, Head of the Research Centre of Medical Genetics, Head of the Department of Molecular and Cell Genetics;&nbsp; 1,3Rena A. Zinchenko — MD, PhD, Professor, Deputy Director of the Scientific and Clinical Study, Head of the Laboratory of Genetic Epidemiology.&nbsp; 1Research Center of Medical Genetics. 1, Moskvorechie str., Moscow, 115522, Russian Federation.&nbsp; 2Pirogov Russian National Research Medical University. 1, Ostrovityanova str., Moscow, 117997, Russian Federation.&nbsp; 3Moscow Regional Research and Clinical Institute. 61/2, Shchepkina str., Moscow, 129110, Russian Federation.&nbsp; Contact information:&nbsp;Vitalii V. Kadyshev, e-mail:&nbsp;[email protected].&nbsp;Financial Disclosure:&nbsp;no author has a financial or property interest in any material or method mentioned. There is no&nbsp;conflict of interests. Received&nbsp;06.12.2018.<br

Epidemiology of hereditary eye disease in the populations of Russian Federation

V.V. Kadyshev1, E.K. Ginter1, S.I. Kutsev1, Zh.G. Oganezova1,2, R.A. Zinchenko1,3 1Research Center for Medical Genetics, Moscow, Russian Federation 2Pirogov Russian National Research Medical University, Moscow, Russian Federation 3N.A. Semashko National Research Institute of Public Health, Moscow, Russian Federation Aim: genetic epidemiological study of hereditary eye diseases in various populations of the Russian Federation and comparative analysis of these findings. Patients and Methods: the sample included 12 ethnic groups from 14 regions of European Russia. The entire population irrespective of gender or age was examined. To confirm a certain type of inheritance of diseases from heterogeneous groups, the material was subjected to the multicomponent analysis used in multiple family registration. The rate of segregation was evaluated using the Weinberg proband method. Molecular genetic tests (Sanger sequencing, MLPA, AFLP, RFLP, whole exome sequencing) were applied. To identify the cases of hereditary disease accumulation in individual populations and/or ethnic groups, the prevalence of certain diseases in this population was calculated using F-distribution to compare the samples of rare diseases. Results: more than 46,000 patients and their relatives with presumably hereditary conditions were examined and data were collected. 554 clinically diverse hereditary diseases in 9,979 individuals were identified. Isolated hereditary eye disease (60 clinical variants) was identified in 1,407 patients (14.56%). The mean prevalence of isolated hereditary eye disease was 1:2,272 (or 44.01 per 100,000). When assessing patterns of nosological spectrum and prevalence of isolated hereditary eye disease in each population/ethnic group using principal component analysis, 2 clusters were isolated. The first cluster includes 6 Russian populations and the second cluster includes 5 ethnic Volga Region groups, which are more similar to Russian populations than the North Caucasus people. In general, 57 hereditary syndromes (affecting anterior and posterior eye segments) in 1,051 patients were discovered. The mean prevalence of syndromic hereditary eye disease was 1:3,040 (or 32.89 per 100,000). Keywords: ophthalmogenetics, genetic epidemiological study, spectrum, ethnic grou p, type of inheritance, segregation, accumulation, isolated and syndromic hereditary eye diseases, prevalence, retinal degeneration. For citation: Kadyshev V.V., Ginter E.K., Kutsev S.I. et al. Epidemiology of hereditary eye disease in the populations of Russian Federation. Russian Journal of Clinical Ophthalmology. 2022;22(2):69–79 (in Russ.). DOI: 10.32364/2311-7729-2022-22-2-69-79. <br

Перкутанный остеосинтез проксимального отдела плечевой кости блокируемыми спицевыми конструкциями

Relevance of a problem. The problem of the choice of an operational method of treatment of multifragmentary fractures of proximal department of a humeral bone remains open still. Aim: improvement of results of treatment of the closed multifragmentary fracture of a humeral bone at the level of a surgical neck with shift of fragments by use of the intense blocked spoke osteosynthesis. Materials and methods. In work the comparative analysis of various methods of expeditious treatment of multifragmentary fracture of a humeral bone in a proximal part at 98 patients with use of clinical, functional and tool methods is carried out. Results and discussion. It is shown that carrying out the intense blocked spoke osteosynthesis minimized a pain syndrome and provided conditions to start the rehabilitational actions including physiotherapy exercises and massage in the first days after operation, reduced need for use of agents of an external immobilization, promoted more complete and fast recovery of volume of movements in a shoulder joint and function of the damaged arm in comparison with an intramedulyarny osteosynthesis by means of pegs both an open reposition and bracing of fragments a nakostny plate. Conclusions. The technique of the intense blocked spoke osteosynthesis can be applied both at the isolated shoulder injury, and at the combined trauma as a low-traumatic way of surgical treatment at patients with fractures of the lower extremities in combination with fractures of proximal department of a brachium.Актуальность проблемы. Проблема выбора оперативного метода лечения многофрагментарных переломов проксимального отдела плечевой кости остается открытой до сих пор. Цель исследования: улучшение результатов лечения закрытого многофрагментарного перелома плечевой кости на уровне хирургической шейки со смещением отломков путем использования напряженного блокируемого спицевого остеосинтеза. Материалы и методы. В работе проведен сравнительный анализ различных методов оперативного лечения многофрагментарного перелома плечевой кости в проксимальной части у 98 пациентов с использованием клинических, функциональных и инструментальных методов. Результаты и обсуждение. Показано, что проведение напряженного блокируемого спицевого остеосинтеза минимизировало болевой синдром и обеспечивало условия для начала реабилитационных мероприятий, включающих лечебную физкультуру и массаж, в первые сутки после операции, снижало необходимость в использовании средств внешней иммобилизации, способствовало более полному и быстрому восстановлению объема движений в плечевом суставе и функции поврежденной руки по сравнению с интрамедулярным остеосинтезом с помощью штифтов и открытой репозицией и фиксацией отломков накостной пластиной. Выводы. Методика напряженного блокируемого спицевого остеосинтеза может применяться как при изолированной травме плеча, так и при сочетанной травме как малотравматичный способ хирургического лечения у пациентов с переломами нижних конечностей в сочетании с переломами проксимального отдела плеча

СРАВНИТЕЛЬНАЯ ХАРАКТЕРИСТИКА РЕЗУЛЬТАТОВ ЛЕЧЕНИЯ МНОГОФРАГМЕНТАРНОГО ПЕРЕЛОМА ПЛЕЧЕВОЙ КОСТИ РАЗЛИЧНЫМИ МЕТОДАМИ ОСТЕОСИНТЕЗА

Aim: to evaluate the effectiveness of treatment of patients with fractures of the proximal humerus with the use of intense blocked spoke osteosynthesis in a comparative aspect with other modern methods of osteosynthesis. Materials and methods: 98 case histories of patients with the diagnosis "closed fracture of humerus at the level of surgical neck with displacement of fragments" aged from 27 to 89 years (22 men and 76 women, mean age 58.6±12.8 years) were analyzed prospectively. Group I (main) consisted of 36 patients who underwent surgical treatment by the method of"intense blocked spoke osteosynthesis". Group II was composed of 31 patients with intramedullary osteosynthesis pin. Group III consisted of 31 patients with fixation of fragments by the plate. Clinical data, laboratory and instrumental data were evaluated. Assessment of the functional status of the affected joint before the surgery was carried out a scale of the Mattis-Luborzyca-Schwarzberg before surgery and on 1, 15, 30, 90 and 180 days after surgery. The assessment of quality of life was performed using the SF-36 questionnaire. Results. It was found that the treatment of fractures of the proximal humerus by the method of strained blocked spoke osteosynthesis significantly increases the effectiveness of treatment of victims compared with intramedullary osteosynthesis pins and bone osteosynthesis plates. Reduced need and reduced the time of immobilization to 7-14 days. By day 14, the majority of patients in group I recovered the volume of joint movements in most patients, in groups II and III such patients were 68.7 (p=0.0001) and 77.7% (p=0.00001), respectively less. The terms of pain relief were reduced. The function of the damaged limb was restored by 15 days in 80.6% of patients of group I, whereas in group II - only in 22.6 (p=0.000001), and in group III - in 16.1% of patients (p=0.000001). Therapeutic exercise was conducted from 1 day in most patients of group I, in groups II and III, the coverage of rehabilitation measures in the first day was 85 (p=0.000001) and 90.3% (p=0.000001) less. Indicator of the effectiveness of surgical treatment against the development of complications was in group I - 94.4 per cent, in group II - 87,1%, in group III - 80,6%. Summary. The method of spoke blocked a busy osteosynthesis and more effective in the treatment of patients with fractures of the proximal humerus compared with intramedullary osteosynthesis with pins and a plate osteosynthesis plates. It is low-traumatic, has high efficiency and low frequency of complications, provides reliable fixation of fragments including in elderly patients, and full restoration of the function of the damaged limb in the early period after surgery.Цель: оценить эффективность лечения пациентов с переломами проксимального отдела плечевой кости с применением напряженного блокируемого спицевого остеосинтеза в сравнительном аспекте с другими современными методами остеосинтеза. Материалы и методы. Проспективно было проанализировано 98 историй болезни пациентов с диагнозом «закрытый перелом плечевой кости на уровне хирургической шейки со смещением отломков» в возрасте от 27 до 89 лет (22 мужчин и 76 женщин, средний возраст 58,6±12,8 года). Группа I (основная), состояла из 36 пациентов, которым оперативное лечение проведено методом «напряженного блокируемого спицевого остеосинтеза». Группу II составил 31 пациент с интрамедуллярным остеосинтезом штифтами. Группу III составил 31 пациент с фиксацией отломков накостной пластиной. Проводили оценку клинических данных, данных лабораторного и инструментального исследования. Оценку функционального состояния поражённого сустава до операции проводили шкале Маттиса-Любошица-Шварцберга до операции и на 1, 15, 30, 90-е и 180-е сутки после оперативного вмешательства. Оценку качества жизни проводили с применением опросника SF-36. Результаты. Было установлено, что лечение переломов проксимального отдела плечевой кости методом напряженного блокируемого спицевого остеосинтеза существенно повышает эффективность лечения пострадавших по сравнению с интрамедуллярным остеосинтезом штифтами и накостным остеосинтезом пластинами. Уменьшалась потребность и сокращались сроки иммобилизации до 7-14 дней. К 14 дню у большинства пациентов группы I восстанавливался объем движений в суставах у большинства пациентов, в группах II и III таких пациентов было на 68,7 (р=0,0001) и 77,7% (р=0,00001) соответственно меньше. Сокращались сроки купирования болевого синдрома. Функция поврежденной конечности восстанавливалась к 15 суткам у 80,6% пациентов I группы, тогда как в группе II - лишь у 22,6 (р=0,000001), а в группе III - у 16,1% пациентов (р=0,000001). Лечебная физкультура с 1 суток проводилась у большинства пациентов группы I, в группах II и III охват реабилитационными мероприятиями в первые сутки был на 85 (р=0,000001) и 90,3% (р=0,000001) меньше. Показатель эффективности оперативного лечения в отношении развития осложнений составил в группе I - 94,4%, в группе II - 87,1%, в группе III - 80,6%. Выводы. Метод напряженного блокируемого спицевого остеосинтеза обладает большей эффективностью при лечении пациентов с переломами проксимального отдела плечевой кости по сравнению с интрамедуллярным остеосинтезом штифтами и накостным остеосинтезом пластинами. Он малотравматичен, обладает высокой эффективностью и низкой частотой осложнений, обеспечивает надежную фиксацию фрагментов в том числе у пожилых пациентов, и полное восстановление функции поврежденной конечности в ранние сроки после проведения хирургического вмешательства

Clinical and genetic aspects of albinism

V.V.&nbsp;Kadyshev, S.A.&nbsp;Ryazhskaya, O.V.&nbsp;Khalanskaya, N.V.&nbsp;Zhurkova, R.A.&nbsp;Zinchenko Research Center for Medical Genetics, Moscow, Russian Federation Albinism is a clinically and genetically heterogeneous group of hereditary diseases whose pathogenesis is mediated by impaired synthesis of melanin which results in its partial or total loss. Reduced melatonin level clinically manifests as skin, hair, and ocular hypopigmentation. Ocular presentations include hypopigmentation/lack of pigmentation of eye fundus and iris, foveal hypoplasia, low vision, nystagmus and strabismus, photophobia, iris transillumination, and asymmetrical decussation of nerve fibers at the optic chiasm. However, albinism can be a part of more complex genetic syndromes, e.g., Hermansky-Pudlak syndrome or Chediak-Higashi syndrome. These disorders should be identified as early as possible to start therapy to prevent life-threatening conditions. Partial albinism with ocular, skin or hair hypopigmentation not associated with melanogenesis (e.g., Griscelli syndrome, Waardenburg syndrome, Aland Island eye disease, etc.) also occurs. Each case of albinism requir es an accurate molecular genetic diagnosis to provide a personalized treatment approach, predict life expectancy and health status, and plan pregnancy. Keywords: albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, hypopigmentation, clinical polymorphism, genetic heterogeneity. For citation: Kadyshev V.V., Ryazhskaya S.A., Khalanskaya O.V. et al. Clinical and genetic aspects of albinism. Russian Journal of Clinical Ophthalmology. 2021;21(3):175–180 (in Russ.). DOI: 10.32364/2311-7729-2021-21-3-175-180. </p

Clinical And Molecular-Genetic Features Of Congenital Aniridia

Vasilyeva T. A.1, Voskresenskaya A. A.2, Kadyshev V. V.1, Pozdeyeva N. A.2, Marakhonov A. V.1,3, Zinchenko R. A.1,4 1 Research Center for Medical Genetics, Moscow 2 Cheboksary branch of S. Fyodorov Eye Microsurgery Federal State Institution 3 Moscow Institute of Physics and Technology (State University), Dolgoprudny 4 Pirogov Russian National Research Medical University, Moscow Introduction: congenital aniridia (AN) is a Mendelian autosomal dominant disorder (population prevalence 1:57143). AN might occur as a part of WAGR syndrome (~13%). The main diagnostic signs of AN are absence of iris and fovea hypoplasia accompanied by nystagmus. Patients also show other eye structures as well as central nervous system anomalies. AN is caused by heterozygous mutations of the PAX6 gene or chromosome rearrangements of 11p13 region. There are no established correlation between the type of PAX6 mutation and the features of aniridia clinical picture. Aim: the paper is to analyze probable relations between AN clinical features and the type of PAX6 mutation. Patients and Methods: 98 patients with AN from 73 unrelated families with identified small PAX6 mutations (74 patients) and large chromosomal 11p13 deletions (24 patients) were analyzed. Patients were divided into the groups according to the type/location of mutation. Phenotypic traits were referred to the type/location of mutation. Contingency tables 2X2 were analyzed by the exact Fisher test. Results: AN clinical picture associated with loss of function mutations (nonsense, frame shift and splicing) has more severe clinical course. Missense mutations are associated with character phenotype of general sample, however, partial aniridia occurs significantly more often. Phenotypes of patients with chromosomal deletions (without deletions of the 3′ cis-regulatory region), do not differ from that of patients with intragenic mutations. A milder phenotype is observed in patients with deletions of the 3′ cis-regulatory region. Key words: congenital aniridia, PAX6 mutations, chromosome region 11p13 deletions, relationships between mutation type and clinical trait. For citation: Vasilyeva T.A., Voskresenskaya A.A., Kadyshev V.V. at all. Clinical and molecular-genetic features of congenital aniridia // RMJ “Clinical ophthalmology”. 2018;1:7–12. <br

Clinical and genetic characteristics of a total or partial congenital aniridia

N.V. Sukhanova1, V.V. Kadyshev1, T.A. Vasilieva1, A.V. Marakhonov1, L.A. Katargina 2, S.I. Kutsev1, R.A. Zinchenko1,3 1Research Center for Medical Genetics, Moscow, Russian Federation 2Helmholtz National Medical Research Center for Eye Diseases, Moscow, Russian Federation 3N.A. Semashko National Research Institute of Public Health, Moscow, Russian Federation Aim: to assess clinical and genetic correlations between the specific clinical manifestations of congenital aniridia (CA) and the spectrum of mutations in the PAX6 gene (including chromosomal deletions involving the entire PAX6 gene or its regions). Patients and Methods: the study included 83 patients fr om 76 unrelated families with clinical patterns of congenital aniridia. The mean age of patients was 11.5±10.3 years. All patients underwent a comprehensive eye exam, molecular and genetic testing, as well as specialist consultation. To find a genetic cause of CA, the analysis of minor mutations in the PAX6 gene was performed by Sanger sequencing in order to determine the nucleotide sequence of 13 exons and adjacent intronic regions. Also, the number of gene copies of a chromosomal region 11p13 was evaluated by using multiplex reaction of Ligation-dependent Probe Amplification (MLPA) assay. In those cases wh ere a chromosomal deletion involving the WT1 gene was detected, a target fluorescent in situ hybridization (FISH) with a locus-specific DNA-probe for the WT1 gene was carried out to prove the MLPA results. The functional in vitro analysis of the impact of intronic nucleotide sequence variants was performed in the laboratory of functional genomics of the Research Center for Medical Genetics (RCMG) using the original technique. Results: the most common features associated with CA included foveal hypoplasia, nystagmus, disorders of the eye lens, and limbal stem cells deficiency (LSCD). These findings were reported in more than 60% of cases. Partial CA was significantly more prevalent in patients with splice-site mutations (p=0.004996) as compared to other mutation types. Optic nerve hypoplasia (p=0.04779), internal strabismus (p=0.010882), aniridia-associated keratopathy co-occurring with LSCD (p=0.013236) were diagnosed more frequently in patients with nonsense mutations. Secondary glaucoma was a more common finding in patients with the deletion of 3'-cis-regulatory region (p=0.020381). Conclusion: the analysis of genotypic and phenotypic correlations has revealed statistical regularities which may underpin the relationship between the clinical pattern of CA and the types of mutations. Keywords: congenital aniridia, foveal hypoplasia, PAX6, mutations, features of the clinical picture, geno-phenotypic correlations. For citation: Sukhanova N.V., Kadyshev V.V., Vasilieva T.A. et al. Clinical and genetic characteristics of a total or partial congenital aniridia. Russian Journal of Clinical Ophthalmology. 2023;23(1):2–8 (in Russ.). DOI: 10.32364/2311-7729-2023-23-1-2-8. </p

Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia))

M.E. Ivanova1, V.V. Kadyshev2, D.S. Atarshchikov3, I.V. Zolnikova4, N.P. Akchurina4, N.K. Serova5, F.A. Konovalov6, E.R. Lozier6, E.A. Pomerantseva7, N.V. Vetrova7, D. Barh8, L.M. Balashova9,&nbsp;J.M. Salmasi10 1 LLC “Oftalmic”, Moscow, Russian Federation 2 Research Centre for Medical Genetics, Moscow, Russian Federation 3 Central Clinical Hospital under Presidential Affairs, Moscow, Russian Federation 4 Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russian Federation 5 N.N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation 6 Independent Clinical Bioinformatics Laboratory, Moscow, Russian Federation 7 Center for Genetics and Reproductive Medicine “Genetiko”, Moscow, Russian Federation 8 Institute of Integrative Omics and Applied Biotechnology (IIOAB), Bangalore, India 9 Non-profit partnership International Scientific and Practical Center for the Proliferation of Tissues of Russia, Moscow, Russian Federation 10Pirogov Russian National Research Medical University, Moscow, Russian Federation The article describes the clinical case of optic atrophy due to a homozygous mutation in exon 3 of the C19orf12 gene (chr19: 30193863AACAGCCCCCCG&gt; A, rs515726204), the frequency of which in the ExAC control sample is 0.0074. With this mutation, a frameshift occurs at 69-th position (p.Gly69fs, NM_001031726.3), which usually leads to neurodegeneration with the brain iron accumulation (NBIA), type 4 (OMIM: 614298). In described clinical case the main complaint of patient was visual impairment, with magnetic resonance imaging patient revealed only the expansion of the sellar fossa. The vision of 7-year-old boy decreased significantly for 2 years without any apparent reasons, spectacle correction did not give an improvement in vision to 100%. During the examination partial atrophy of the optic nerves was revealed, consultations were conducted with a neurologist, neurophthalmologist. Hyperreflexia, gait changes, and a slight delay in speech development were also revealed. No other clinical neurological symptoms were observed. The article describes a detailed ophthalmic clinical picture, discusses diagnostic and therapeutic tactics. Keywords: optic nerve atrophy, neurodegeneration with the brain iron accumulation, NBIA, mutation, gene, C19orf12. For citation: Ivanova M.E., Kadyshev V.V., Atarshchikov D.S. et al. Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia)). Russian Journal of Clinical Ophthalmology. 2020;20(1):–36. DOI: 10.32364/2311-7729-2020-20-1-33-36. </p