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

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА НАСЛЕДСТВЕННЫХ ФОРМ ВРОЖДЕННОЙ АНИРИДИИ С ПОЗИЦИЙ СОВРЕМЕННОЙ ГЕНЕТИКИ

Congenital aniridia (AN) is a hereditary autosomal dominant developmental disorder of the eye. Heterozygous mutations in the PAX6 gene and chromosomal rearrangements involving the 11p13 locus lie behind the pathogenesis of the AN. The key role of the PAX6 gene in the regulation of embryogenesis and the pleiotropic effect of this transcription factor explain the damage of several tissues of the anterior and posterior segments of the eye, brain structures, and the disturbance of morphogenesis and endocrine function of the pancreas observed in AN. Recently AN has been considered a syndromic pathology by several researchers. The review suggests classification and summarizes information on the clinical characteristics and genetic basis of various forms of AN. The problem of discrimination of clinical-genetic variants of the dysgenesis of the anterior segment of the eye and the differential diagnosis of PAX6-associated AN with WAGR syndrome, anterior dysgenesis, other rare monogenic and chromosomal syndromes is discussed, and the role of molecular diagnostics is emphasized.Врожденная аниридия (ВА) — наследственный аутосомно-доминантный порок развития глаз. В основе патогенеза ВА лежат гетерозиготные мутации в гене PAX6 и хромосомные перестройки, вовлекающие локус 11p13. Ключевая роль гена PAX6 в регуляции эмбриогенеза и плейотропность действия этого транскрипционного фактора объясняют возможность поражения сразу нескольких сред переднего отрезка глаз и глазного дна, структур головного мозга, а также нарушение морфогенеза и эндокринной функции поджелудочной железы, наблюдаемые при ВА. В последнее время ВА стала рассматриваться рядом исследователей как синдромальная патология. В обзоре собраны сведения о клинической характеристике, генетической основе различных форм ВА. Обсуждается проблема дискриминации клинико-генетических вариантов дисгенезии переднего отрезка глаза и дифференциальной диагностики PAX6-ассоциированной ВА с синдромом WAGR, дисгенезиями переднего отрезка глаз, другими редкими моногенными и хромосомными синдромами; подчеркивается роль молекулярной диагностики

Spin alignment of K∗(892)±K^*(892)^\pm mesons produced in neutron-carbon interactions

A new precise measurements of spin density matrix element $\rho_{00}$ of $K^*(892)^{\pm}$ mesons produced inclusively in neutron-carbon interactions at \~60 GeV have been carried out in the EXCHARM experiment at the Serpukhov accelerator. The values of $\rho_{00}$ obtained in the transversity frame are $0.424\pm0.011(stat)\pm0.018(sys)$ for $K^*(892)^+$ and $0.393\pm0.025(stat)\pm0.018(sys)$ for $K^*(892)^-$. Significant $P_T$ dependence of $\rho_{00}$ has been observed in $K^*(892)^+$ production.Comment: 8 pages, LaTeX, 3 eps figure

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

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