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Objective: to identify molecular genetic predictors of metastatic spread to regional lymph nodes in patients with breast cancer (BC) based on the analysis of gene expression profile of the primary tumor.Materials and methods. The study included 358 patients with BC who underwent surgical treatment in breast cancer department of Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. Among all included into the study patients, 132 (36.9 %) had metastases in at least one axillary lymph node. Molecular genetic examination of the tumor tissue was carried out using reverse transcription polymerase chain reaction; the diagnostic panel consisted of 45 functional and 3 reference genes. Results. Patients with metastases to regional lymph nodes were generally younger (p = 0.006), had larger primary tumor (pConclusion. TMEM45A, CCND1 and MIA gene expression in the primary tumor were the markers of lymph node involvement in BC. The developed predictive genetic signature can become an additional diagnostic tool to predict the risk of lymph node metastases at the point of planning the volume of axillary surgery in patients with BC.

The article is devoted to the study of forensic genetic examination in civil proceedings as an object of constitutional protection, due to the emergence of the concept of forensic examination in general and forensic genetic examination, entities entitled to conduct forensic examinations, analyzing the legal basis of court - genetic examination in Ukraine. Characteristics of the legal basis for recognition of paternity/mother and establishing the fact of paternity/mother are presented. The admissible and appropriate evidence bases in such cases and the place of forensic genetic examination in in the system of evidence that can be involved in the case have been clarified. The features of this examination have been studied, basis to proceed with the molecular genetic examination, the grounds for conducting a molecular genetic examination have been determined, and the issues raised before the expert carrying out the expert research have been singled out. The analysis of judicial practice of consideration of cases on recognition of paternity/maternity and the establishment of the fact of paternity/maternity which is carried out with carrying out forensic genetic examination was carried out. The article analyzes the problematic issues that arise in the process of legal regulation of forensic genetic examination and the practice of applying legislation in this area. The problems of evasion of a party from participation in forensic genetic examination, namely, non-appearance at a certain time to participate in the examination, failure to provide materials for expert research and the legal consequences of such evasion for all participants in the case. This article offers ways to solve problematic aspects of the research. The conclusions on the application by the courts of the results of forensic genetic examination during the consideration of cases on recognition of paternity/maternity, establishment of the fact of paternity/maternity were generalized and made. Forensic genetic examination is an individual identify. This type of examination allows not only to categorically exclude paternity, but also to carry out the origin of the child from both parents due to blood relationship (identification), as well as the diagnosis of hereditary diseases in the fetus in the early stages of pregnancy. Conducting such an examination is an effective mechanism of constitutional protection, because the facts established as a result of the examination form the basis of the evidence base are considered in conjunction with other evidence available in the case file.

The article is focused on the procedure of sampling as a criminal procedural action necessary for the commissioning and carrying out molecular genetic expert examination in the divisions of the Expert Service of the Ministry of Internal Affairs, namely the establishment and comparison of genetic traits of living and dead persons and unidentified corpses within criminal proceedings and civil cases for establishing or refutation of the fact of paternity. The purpose of the work is to provide information about human biological material that can be used as samples for molecular genetic research of living and dead people and unidentified corpses; analysis of errors during sampling of biological material of individuals for each type of samples and determining the methods of storage and transportation of research objects depending on their condition. The author has studied the legal aspects of the procedure of selecting the samples of biological origin according to the rules of identity examination and has indicated the list of documents required for sampling relatives of missing persons for the placement in the central database of human genetic traits. The author has specified the basic requirements for sampling, such as their indisputable belonging to a certain person and reliability of their selection in the minimum quantity necessary for the research. The information that should be indicated on the packaging of biological material has been described. The types of biological material that can be provided for the research as living specimens have been separately studied, namely: nails, blood, buccal epithelium, saliva, which can be provided on a piece of sterile gauze, FTA Cards, cotton, viscose or flock sticks or probe swabs. The author has also defined the persons who have the right to carry out selection from living persons, conditions of selection, drying of samples, possibilities of their long-term storage and conditions of transportation to divisions of the Expert Service of the Ministry of Internal Affairs of Ukraine. Errors in selecting the packaging of biological material (catheters with heparin filling, Ames medium, polymer containers) have been analyzed. Blood, bone remains, teeth, nails and histological specimens have been studied as types of biological material taken from dead persons and unidentified corpses depending on the condition of the remains, environmental conditions and prescription of death coming.

The term “personalized medicine” appeared only 20 years ago, but individual approaches to the therapy were known for more than a hundred years. The genome decoding and development of pharmacogenetics in recent decades have opened up new ways for the development of medicine and a new understanding of the concept of “personalized medicine”. The article uses the example of nephrological diseases (Denis–Drash syndrome, Freiser syndrome, hypophosphatemic rickets, nephrotic syndrome) to demonstrate the importance of molecular genetic examination and to improve the effectiveness of treatment and, most importantly, to prevent iatrogenic side effects of the therapy. The example of glucocorticoid therapy of children with nephrotic syndrome is used to demonstrate the importance of studying certain genetic factors that affect the individual pharmacodynamic and pharmacokinetic profile of glucocorticosteroids.

The article is devoted to the urgent problem of neonatology and pediatric neurology — seizures in newborns and young children. In the work, a short review of the clinical and genetic characteristics of monogenic epilepsy is presented, in particular, the main attention is paid to the variants that begin in neonatal and early childhood. It has been shown that a significant number of epileptic encephalopathies are caused by mutations in genes whose protein products form voltage-dependent (sodium and potassium), ligan(dependent (γ-aminobutyric acid — GABA) channels, the functioning of which ensures the passage of a nerve impulse in neurons of the cerebral cortex. The necessity of including the molecular genetic methods into the algorithm for examining a child with epilepsy, in particular with epileptic encephalopathy, is emphasized. It is noted that congenital metabolic disorders are one of the etiological reasons for the development of epileptic seizures in children, in particular in newborns and young children. It was shown that congenital metabolic disorders have phenotypic manifestations of epileptic encephalopathy. Some curable metabolic defects that are accompanied by seizures, their diagnosis and timely treatment are described. No conflict of interest was declared by the authors. Key words: newborn, epilepsy, epileptic encephalopathy, diagnosis, genetic examination, metabolic defects, review.

The features of the clinical course of non-compaction cardiomyopathy, its prognosis and even its diagnosis are still the subject of discussion. The variety of phenotypes of this disease and genetic heterogeneity dictates the need for detailed clinical and molecular genetic examination of patients with this pathology. The article presents a clinical observation of a patient with a dilated phenotype of left ventricular non-compaction, progression of chronic heart failure, as well as the presence of ventricular rhythm and conduction disorders that required the implantation of cardiac resynchronization therapydefibrillator (CRT-D). The patient was found to have a missense mutation c. 1892A>G (p.Tyr631Cys, rs1060501183) in PKP2 gene in a heterozygous state. The issues of differential diagnostics with arrhythmogenic right ventricular cardiomyopathy and treatment strategies for the disease were discussed.

Zenker carcinoma is still being treated empirically because of the lack of evidence‐ based guidelines. We report for the first time about the genetic examination of this rare entity. The revealed mutations show genetic similarities with HPV(‐)HNSCC which suggests that well‐known therapeutic strategies may be applicable for this disease, The TP53 gene and its mutations in HNSCC (yellow), in hypopharynx (orange) and in Zenker carcinoma (red).

A qualitative improvement in the management of pregnancy and delivery, optimization of General care and provision of intensive care for children born prematurely, particularly with low and extremely low body weight, significantly reduced the risk of damage to the nervous system of perinatal hypoxic-ischemic genesis. At the same time, there is a significant number of children born at low gestational age, with a significant violation of intellectual, cognitive development and behavior change. One of the assumptions about cause of improper maturation of the brain is the role of unbalanced chromosomal and genomic micro anomalies. There is provided the data on the survey of 22 children with approximately the same clinic of developmental disorders, 19 of which revealed various structural micro-damages of genesis, but their interpretation is difficult today. The algorithm of selection of children for the extended genetic examination is given.

To study the prevalence of mutations in the GJB2 gene in deaf and deaf children in the Astrakhan region and compare them with the frequency of mutations in children with hearing impairment living in other regions of the Russian Federation taking into account regional characteristics. This work describes the results of epidemiological, audiological analysis, medical and genetic examination of children. We examined 6 frequent recessive mutations in the GJB2 gene in a group of 79 hearing impaired children registered with the Regional Center for Hearing Rehabilitation. Mutations were detected in 36 children (46%), with two mutations found only in 18 children (23%), and another 18 children were carriers of the same mutation. In 9 children (11.5%), the 35 delG mutation was detected in the homozygous state and in 9 children (11.5%) in the compound heterozygous state with a different mutation. We have shown that the results obtained do not correspond to the high prevalence of gene mutations (more than 50%) in groups of children with hearing impairment, established in most regions of the Russian Federation, as well as in several countries in Europe, China and Japan. The large number of carriers of a single gene mutation indicates the need to study the entire gene sequence and may be a consequence of the mixed ethnic composition of the subjects.

OBJECTIVE The aim: To carry out a historical review of the formation and development of medical forensics in the XIX - early XX century in Ukraine, as well as to identify its trends at the present stage. PATIENTS AND METHODS Materials and methods: The article is based on the study of archival and published materials, the results of integrating expert judgments, judicial practice and regulatory acts of the Ministry of Health of Ukraine, interviewing investigators and court experts. In the course of the research a system of scientific methods has been used: historical, comparative, terminological analysis, formal-logical, sociological. CONCLUSION Conclusions: In the XIX and early XX centuries, the foundations for the formation of medical criminalistics were laid, which facilitated the development of forensic medicine, criminalistics and forensic examination. Special medical knowledge is widely used in investigative, judicial and expert practice. The synthesis of medical and forensic knowledge enhanced the development of a method of personal identification, based on his/her genetic properties, the formation of molecular genetic examination, the study of individual objects at the modern level.

Fanconi anaemia (FA) is a rare genetic abnormality. Most of FA reported from the sub-Saharan population came from southern Africa, with many patients linked to a mutation in the FANC G gene. Classic triads of this disorder are: a varied malformation, bone marrow failure, and short stature. This disorder is also associated with predisposition to malignancies. These multiple manifestations, sometimes not uniform, often cause diagnostic delay. We here report a 13-year-old Senegalese boy with FA. He was followed up for polydactyly-repair surgery. Importantly, pre-operative blood check-up revealed severe anaemia, which prompted us to perform bone marrow aspiration: examination revealed dysmyelopoiesis. Being triggered by this, systematic examinations were performed, which revealed other signs indicative of FA; i.e., radial spine abnormalities, triangular face, etc. The diagnosis of FA was strongly suggested, which prompted genetic examination. The chromosomal breakage test detected cellular hypersensitivity to DNA, which confirmed the diagnosis. He is receiving transfusion support, and androgens use is being considered. This case highlights the importance of preoperative examination. Physicians must be aware that FA, although its incidence is low, can be hidden behind infantile anaemia.

Restrictive cardiomyopathy often results in chronic heart failure. Knowledge of family history and genetic examination are extremely important for the early diagnostics of a family restrictive cardiomyopathy and prescription of non-specific therapy. The article describes clinical case of familial restrictive cardiomyopathy with a burdened family history.

Summary: Objective: The main objective of the article is to clearly inform healthcare professionals about the newly implemented molecular classification of endometrial cancer into practice. Methods: Summary of current knowledge, recommendations and new procedures relating to molecular genetic examination of the tissues of patients with endometrial carcinoma. Results: Endometrial cancer is currently diagnosed on the base of histopathological morphology. According to the classical Bokhman division, we distinguish between two relatively wide groups of tumors which are different in pathogenesis: type I – estrogen-dependent tumors, clinically usually indolent, and type II – non-endometroid tumors, clinically aggressive, without dependence on estrogen stimulation. This classification fulfills a didactic purpose and provides easy orientation for epidemiological data, but is not suitable for stratification due to the overlap of clinical, pathological and molecular features. The Cancer Genome Atlas project classifies endometrial tumors into 4 groups based on molecular genetic features. Conclusion: Integration of the histopathological findings along with molecular classification appears to be the best approach for evaluating each individual tumor. This will help to achieve the ideal stratifi cation of patients for treatment regimens.

Purposes: To study the clinical and genetic background of a series of Italian patients affected by pattern dystrophy (PD).Methods: We reviewed patients with a clinical diagnosis of PD examined at the Eye Clinic in Florence from 2012 to 2019. We took into consideration patients with a standard ophthalmological examination, personal and familial ophthalmological history, fundus imaging, and molecular genetic analysis of genes PRPH2 and BEST1. We labelled patients with BEST1 and PRPH2 mutations as m-PD group (mutated) whereas patients with no mutations in these 2 genes as nm-PD group (non-mutated).Results: Seventy-seven PD patients were assessed (average age 59.7 ± 14.2, range 31-88 years). Fifty patients were placed in the nm-PD group and 27 in the m-PD. Pathogenic BEST1 and PRPH2 mutations were detected in 7% and 22% of PD patients, respectively. In total, we reported 1 BEST1 and 8 PRPH2 novel mutations. Ten patients were characterized by drusen in the nm-PD group whereas in no patients in the m-PD group drusen were detected at the fundus.Conclusions: An important proportion of patients affected by PD showed BEST1 or PRPH2 mutations. Patients affected by drusen represent a different sub-phenotype. Genetic examination is recommended for a correct clinical management.

In the work, a short review of the clinical and genetic characteristics of monogenic epilepsy is presented, in particular, the main attention is paid to the variants that begin in neonatal and early childhood. It has been shown that a significant number of epileptic encephalopathies are caused by mutations in genes whose protein products form voltage-dependent (sodium and potassium), ligan(dependent (γ-aminobutyric acid — GABA) channels, the functioning of which ensures the passage of a nerve impulse in neurons of the cerebral cortex. The necessity of including the molecular genetic methods into the algorithm for examining a child with epilepsy, in particular with epileptic encephalopathy, is emphasized. It is noted that congenital metabolic disorders are one of the etiological reasons for the development of epileptic seizures in children, in particular in newborns and young children. It was shown that congenital metabolic disorders have phenotypic manifestations of epileptic encephalopathy. Some curable metabolic defects that are accompanied by seizures, their diagnosis and timely treatment are described. No conflict of interest was declared by the authors., Статья посвящена актуальной проблеме неонатологии и детской неврологии — судорогам у новорожденных и детей раннего возраста. Представлен короткий обзор клинико(генетических характеристик моногенных эпилепсий, в частности, основное внимание обращено на варианты, которые начинаются в неонатальном и раннем детском возрасте. Показано, что значительное количество эпилептических энцефалопатий обусловлено мутациями в генах, белковые продукты которых формируют вольтаж-зависимые (натриевые и калиевые), лиганд-зависимые (γ-аминомаслянная кислота — ГАМК) каналы, функционирование которых обеспечивает прохождение нервного импульса в нейронах головного мозга. Подчёркнута необходимость включения молекулярно-генетических методов в алгоритм обследования ребенка с эпилепсией, в частности, с эпилептической энцефалопатией. Отмечено, что врожденные нарушения метаболизма являются одной из этиологических причин развития эпилептических припадков у детей, в частности, у новорожденных и детей раннего возраста. Показано, что врожденные нарушения метаболизма имеют фенотипические проявления эпилептической энцефалопатии. Описаны отдельные курабельные дефекты метаболизма, которые сопровождаются судорогами, их диагностика и лечение. Авторы заявляют об отсутствии конфликта интересов., Стаття присвячена актуальній проблемі неонатології та дитячої неврології — судомам у новонароджених та дітей раннього віку. Наведено короткий огляд клініко(генетичних характеристик моногенних епілепсій, зокрема, основну увагу звернено на варіанти, які розпочинаються в неонатальному та ранньому дитячому віці. Показано, що значна кількість епілептичних енцефалопатій зумовлена мутаціями в генах, білкові продукти яких формують вольтаж-залежні (натрієві та калієві), ліганд-залежні (γ-аміномасляна кислота — ГАМК) канали, функціонування яких забезпечує проходження нервового імпульсу в нейронах головного мозку. Наголошено на необхідності введення молекулярно-генетичних методів до алгоритму дослідження дитини з епілепсією, зокрема, епілептичною енцефалопатією. Означено, що вроджені порушення метаболізму є однією з етіологічних причин розвитку епілептичних нападів у дітей, зокрема, у новонароджених та дітей раннього віку. Показано, що більшість епілепсій при вроджених дефектах метаболізму мають фенотипові ознаки епілептичної енцефалопатії. Описано окремі курабельні дефекти метаболізму, які супроводжуються судомами, їх діагностику та лікування. Автори заявляють про відсутність конфлікту інтересів.

Целью исследования было изучение спектра и выявление этнических особенностей мутаций гена РАН у пациентов с ФКУ в Казахстане. В статье представлены результаты молекулярно-генетического обследования 88 пациентов с ФКУ из неродственных семей, из них 36 пациентов казахской национальности, 44 русских, 5 уйгуров и 3 узбека. Наиболее частой мутацией в гене РАН у казахов была мутация p.243Q (с частотой 0,250), у русских, уйгур и узбеков - мутация p.R408W с частотой 0,545, 0,400 и 0,333 соответственно. Только у казахов были выявлены следующие мутации в гене РАН: IVS4+5G>T, IVS10-14C>G (0,028), p.V230I (0,028), p.A300S (0,014), p.W187X (0,014), p.R158Q (0,014), p.Y387H (0,014), p.I65N (0,014), p.R243L (0,014), p.Val399= (0,014), c.326e>G (0,014), p.P119S (0,014). Мутации IVS7-3C>A и p.E390G гена РАН были обнаружены только у русских. Для пациентов уйгурской национальности этнически специфичной оказалась мутация p.R413P, для узбеков - мутации p.R261X, G188D, p.R252Q, c.826-829 ins/del4?. Полученные результаты позволили описать спектр и этнические особенности мутаций гена РАН в Казахстане. The aim of the study was to study the spectrum and identify ethnic characteristics of mutations of PAH gene in patients with PKU in Kazakhstan. The article presents the results of molecular genetic examination of 88 patients with PKU from unrelated families, including 36 patients of Kazakh nationality, 44 Russians, 5 Uighurs and 3 Uzbeks. The most frequent mutation in the PAH gene in Kazakhs was p.243Q mutation (with a frequency of 0.250), in Russians, Uighurs and Uzbeks p.R408W mutation with a frequency of 0.545, 0.400 and 0.333, respectively. Only in Kazakhs, following mutations were identified in PAH gene: IVS4 + 5G> T, IVS10-14C> G (0.028), p.V230I (0.028), p.A300S (0.014), p.W187X (0.014), p.R158Q (0.014), p.Y387H (0.014), p.I65N (0.014), p.R243L (0.014), p.Val399 = (0.014), c.326e> G (0.014), p.P119S (0.014). Mutations IVS7-3C> A and p.E390G in PAH gene were found only in Russians. For patients of Uyghur nationality, mutation p.R413P turned out to be ethnically specific; for Uzbeks, the mutations p.R261X, G188D, p.R252Q, c.826-829 ins/del4?. The results obtained allowed us to describe the spectrum and ethnic characteristics of mutations of PAH gene in Kazakhstan.

Транссексуализм - многофакторное нарушение формирования пола, этиология и патогенез которого, недостаточно изучены. В работе представлены результаты комплексного клинического и медико-генетического обследования 55 пациентов с транссексуализмом (ТС), проанализированы данные собственных цитогенетических исследований и исследования состояния гаметогенеза. Transsexualism is a gender identity disorder with a multifactorial etiology and poor understood pathogenesis. The study presents the results of a comprehensive clinical and genetic examination of 55 patients with transsexualism, cytogenetic data and results of quantitative analysis of gametogenesis are evaluated.

The question of whether it is appropriate to classify genetic examinations of kinship as a medical service is considered in the article. Establishment of identity of an unknown individual (alive or dead) with a specific person is a classic example of forensic medical genetic examination. At the same time an examination on establishment of biological kinship of people whose identity is known and doesn’t demand identification cannot be classified as an identificational. That is the study of human DNA to establish kinship cannot be referred to as a class of medical examinations. Forensic medical examination (including genetic) is a type of medical activity which is carried out by a medical organization and therefore needs licensing. However, if an examination is not carried out in a medical organization and there is no word “medical” in the name such an examination cannot be considered as a medical activity and doesn’t need licensing exactly as it is arranged in expert institutions of the Ministry of Internal Affairs of the Russian Federation at this point. Such examinations can be considered as a type of forensic biological expertise.

The article describes a clinical case of early diagnosis of hereditary thrombophilia in a child in the neonatal period, based on clinical, laboratory and genetic examination. Clinical suspicion to hereditary hemostatic disorders, careful analysis of hereditary and family history allowed to identify and confirm with the help of PCR polymorphism of genes associated with hemostatic system in a child of two weeks of age. Early diagnosis allows to make an individual plan of observation and dynamic examination to prevent increased thrombosis and possible vascular catastrophe in the child, to prevent metabolic and hemostatic disorders in both the mother and her relatives, and in the probable future siblings of the patient, and in the long term and in his descendants.

The article is devoted to comparing the performance of disinfectants at different concentrations of a contaminating agent. Contamination of objects can occur at any stage of the study, so effective methods of decontamination should be used to prevent it, which at the same time should be safe for laboratory staff. The purpose of the work is to check the effectiveness of disinfectants while working in biological laboratories and to determine their effects on the genetic information of the cell, the effect on the inhibition of PCR reaction and DNA degradation. The mechanisms of influence on a cell and DNA of chemical solutions are analyzed: Винсепт експресс, Бациллол АФ, Дезактин 0, 2 %, WIP'ANIOS Premium, DNAZap™ PCR DNA Degradation Solutions, 70 % и 96 % ethyl alcohols, and physical methods: ultraviolet radiation, alcohol treatment followed by calcination in the flame of the burner and treatment with bidistilled deionized water. While research the contaminating DNA is represented by the synthetic genomic DNA produced by the Promega company. As a result of the pilot study, DNAZap ™ PCR DNA Degradation Solutions and bidistilled deionized water had the highest decontamination efficiency. Bidistilled deionized water can be used to the fullest in the laboratory if medical waste disposal standards are met. Other methods showed an efficiency of more than 99.98% which also allows them to be used when working in a biological laboratory, following the suggested recommendations. The presented methods of decontamination did not cause inhibition of the PCR reaction. Preserved, after decontamination treatment, DNA for most agents had a low level of degradation. After being treated with ultraviolet radiation, the level of DNA degradation was medium which means that ultraviolet radiation destroys long strands of DNA, leaving strands unbroken up to 200 bp. In addition, increasing the concentration of contaminating DNA did not affect the change in the efficiency of decontamination substances. All the decontaminated substances analyzed can be modified in molecular genetic laboratories.

Resumen La debilidad producida por la patologia del musculo o de la transmision neuromuscular tiene multiples causas. La aproximacion a este problema comienza por una anamnesis exhaustiva y sistematica que identifique patron de herencia, factores desencadenantes, edad y forma de inicio y sintomas especificos. La exploracion neurologica y general nos aportara datos fundamentales para ir restringiendo las posibilidades diagnosticas. Los estudios neurofisiologicos son una extension de la exploracion clinica, pueden sugerir el origen miopatico y son diagnosticos en las enfermedades de la transmision neuromuscular. Distintos anticuerpos son diagnosticos en enfermedades como miopatias inflamatorias o miastenia gravis. La biopsia muscular muestra rasgos caracteristicos de distintas miopatias y puede ser diagnostica o reducir el diagnostico diferencial a unas cuantas entidades. En las miopatias hereditarias y sindromes miastenicos congenitos, el diagnostico de certeza viene dado, muchas veces, por el estudio genetico que identifica el defecto molecular subyacente. Several causes are involved on muscle or neuromuscular transmission disorders causing muscle weakness. Exhaustive and systematic anamnesis, looking for inheritance pattern, triggering factors, age, onset form and specific symptoms, constitute the first approach. Neurological and general examination will bring us fundamental data focusing diagnostic alternatives. Neurophysiological tests, as an extension of the clinical exploration, can suggest myopathic origin, as well as they are a diagnostic tool for neuromuscular transmission disorders. In some cases, serological tests allow the diagnosis of several inflammatory myopathies or myasthenia gravis. In other myopathies, muscle biopsy shows characteristic features playing diagnostic role or supporting differential diagnosis. The certainty for diagnosis of inherited myopathies and congenital myasthenic syndromes is achieved, in many cases, by genetic examination revealing underlying molecular defect.

Within the project MedPed (Make Early Diagnosis to Prevent Deaths) we have examined patient with familial hypercholesterolemia in our lipid ambulance. During the following investigation of the patients family we found out that her sister has on the contrary very low levels of total and LDL-cholesterol. Concentration of HDL-cholesterol was extreamly low (almost immeasurable). Differential diagnosis uttered a suspicion of rare form of familial hypoalfalipoproteinemia so-called Tangier disease. This suspicion was then confirmed by molecular genetic examination. Tangier disease is a rare lipoprotein metabolism disorder characterized biochemically by almost complete absence of plasmatic HDL- cholesterol, extremely low level of apolipoprotein A-I and accumulation of cholesterol esters in macrophages. The first case was recorded on the Tangier island in 1961. In our research we describe the first case of a patient with homozygous form of Tangier disease in the history of the Czech Republic.

This article examines the role of the typewriter in the genetic process of the novel Vuosisatain vaatimus (1918) by the Finnish novelist Jalmari Finne (1874–1939). Finne is a rare example of an early twentieth-century author who mastered touch typing and composed directly on a typewriter. He claimed that he used the typewriter because it enabled him to keep up with his thinking, a claim that challenges Friedrich Kittler’s (1990, 193) thesis that the most remarkable feature of the typewriter is not its speed but its “spatially and discrete signs”. A genetic examination of Finne’s typescripts suggests that he had developed generative typing into a kind of “blind revision” in that he did not read and correct previous drafts but rather inserted a blank paper in the machine and typed an altogether new version of the text without copying the previous version.

Рассматривается одна их актуальнейших проблем семейного права и гражданского судопроизводства проблема установления отцовства. Определяется специфика доказывания по делам об установлении отцовства. Особенности определения отцовства с применением современных методов генетической экспертизы прослеживаются на конкретных примерах из судебной практики., One of the most urgent problems of family law and civil proceedings is considered - the problem of establishing paternity. The specificity of evidence in cases of establishing paternity is determined. Features of the definition of paternity using modern methods of genetic examination are traced on specific examples from judicial practice., №12 (2019)

Hereditary hearing impairment (HHI) is a common but heterogeneous clinical entity caused by mutations in a plethora of deafness genes. Research over the past few decades has shown that the genetic epidemiology of HHI varies significantly across populations. In this study, we used different genetic examination strategies to address the genetic causes of HHI in a large Taiwanese cohort composed of &gt, 5000 hearing-impaired families. We also analyzed the clinical features associated with specific genetic mutations. Our results demonstrated that next-generation sequencing-based examination strategies could achieve genetic diagnosis in approximately half of the families. Common deafness-associated genes in the Taiwanese patients assessed, in the order of prevalence, included GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. However, the Taiwanese patients had some unique mutations in these genes. These findings may have important clinical implications for refining molecular diagnostics, facilitating genetic counseling, and enabling precision medicine for the management of HHI.

The article is devoted to the rare disease of the lysosomal storage disease group – Fabry’s disease. The disease is associated with the sphingolipids dysmetabolism, is caused by the accumulation of the globotriosylceramide (Gb 3 ) and othersphingolipidsin the organism tissues and cells; it is characterized by the progression and severity of the course. The diagnostic results of 6 patient children aged from 5 to 17 years are analyzed; 2 boys and 4 girls from 3 families. The hereditary burden with a large number of the disease cases, 16 patients in 3 families including 6 children, comes under notice. All 6 children were diagnosed with Fabry’s disease based on the genealogical analysis as well as biochemical and molecular genetic examination. The activity of α-galactosidase A enzyme in the blood leukocytes was significantly decreased in two boys, insignificantly decreased in two sisters, and was normal in two girls. When performing the molecular genetic analysis, 3 mutations in exon 5 of GLA gene were identified. It has been established that the damages of cardiovascularsystem and nervoussystem, kidneys and visual organ, depression of the perspiratory gland function shall be considered as the first clinical signs of the disease in the children; it seems likely that the angiokeratoma appearance is characteristic only for boys. The presence of the non-specific symptoms and signs of the connective tissue dysplasia is noteworthy. The emphasis is made towards the importance of the early Fabry’s disease diagnosis, as it is essential for the timely (prior to appearance of the clinical symptoms and signs) beginning of the pathogenic treatment with the enzyme replacement drug.

Objectives: A few adult and adolescent patients with even severe cholestatic liver disease remain unexplained after standard diagnostic work-up. We studied the value of genetic examination in such patients and developed a panel of eight genes with known cholestatic associations. Materials and methods: Thirty-three patients with unexplained cholestasis despite a thorough clinical work-up were examined for sequence variations in the coding regions of the ABCB4, ABCB11, ABCC2, ABCG5, ATP8B1, JAG1, NOTCH2, and UGT1A1 genes and the promoter region of UGT1A1 by massive parallel sequencing of DNA extracted from whole blood. Hepatologists and clinical geneticists evaluated the causal potential of genetic variants. Results: In 9/33 patients (27%), we identified genetic variants as a certain causal factor and in further 9/33 (27%) variants as a possible contributing factor. In most cases, a detailed family history was necessary to establish the importance of genetic variants. Genetic causes were identified in 6/13 women (46%) with intrahepatic cholestasis during pregnancy and persisting abnormal biochemistry after delivery. Conclusions: Our study suggests that a small number of well-known genetic variants are involved in at least 27–54% of patients with unexplained cholestasis. An expanded panel will likely explain more cases. This motivates genetic testing of these patients. Genetic testing, however, cannot stand alone but should be combined with a clinical genetic work-up in collaboration between hepatologists and clinical geneticists.

Patients suffering from mental retardation have a smaller risk of becoming criminals than other people. This is, however, not true for violent crimes: The risk to be prosecuted for violent crime is said to be twice for men, for women it is even twelve times higher than for the average population. This risk is especially high when there is a comorbid psychiatric disorder as e.g. an autism spectrum disorder [1]. Contrary to the average population, the prevalence of aggression is equal for both sexes. Autistic children who are violent have a poor prognosis [2]. This report discusses the case of a young woman suffering from mental retardation and a comorbid autism spectrum disorder who committed a serious violent crime. Since the causes of mental retardation are usually genetically founded [3], I will - after having described the case report and the related diagnostic deliberations - ask questions about the limitations of the usual categorical-descriptive diagnosis, as is usual in current forensic-psychiatric practice.

The article provides a brief literature review on the problem of asymptomatic pancreatic hyperenzymemia and an algorithm for examining patients. The authors for the first time in Ukraine have described the clinical observation of family with Gullo’s syndrome — family benign pancreatic hyperenzymemia. Family members were carefully examined, structural changes in the pancreas were excluded, and its normal functional state was proved. The results of a genetic examination are presented.

Familial glucocorticoid deficiency (FGD, MIM*202200) is a rare form of primary chronic adrenal insufficiency characterized by resistance of the adrenal cortex to ACTH, decrease in secretion of glucocorticoids and adrenal androgens, and increase in plasma ACTH level. Currently, at least 7 genes whose mutations lead to the development of FGD have been described. These are MC2R, MRAP, STAR, CYP11A1, NNT, TXNRD2, and AAAS. E. Meimaridou and J. Kowalczyk were the first who described NNT gene mutation in 2012 in one patient who underwent molecular genetic examination and 9 patients with clinical presentation of familial glucocorticoid deficiency. Understanding of the exact cause of primary chronic adrenal insufficiency enables adjusting the treatment, predicting the development of possible complications and related dysfunctions of other organs, as well as the need for medical and genetic counseling of the family.