scholarly journals THE URGENCY OF GENETIC VERIFICATION OF NON-COMPACTION CARDIOMYOPATHY IN CHILDREN: CLINICAL CASES

2018 ◽  
Vol 17 (2) ◽  
pp. 157-165
Author(s):  
Nataliya A. Sdvigova ◽  
Elena N. Basargina ◽  
Dmitry V. Ryabtsev ◽  
Kirill V. Savostyanov ◽  
Alexander A. Pushkov ◽  
...  
Keyword(s):  
Genetic Disorders ◽  
Systolic Dysfunction ◽  
Venous Blood ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Hereditary Diseases ◽  
Molecular Genetic Study ◽  
Disease Etiology ◽  
Myocardial Diseases ◽  
Clinical Cases

Background. Non-compaction cardiomyopathy is a group of genetically heterogeneous, poorly studied myocardial diseases with a variety of clinical manifestations (from asymptomatic course to progressive systolic dysfunction with symptoms of chronic heart failure, arrhythmias, and thromboembolic complications). Considering the variety of genetic disorders associated with the development of noncompaction cardiomyopathy, genetic verification of the diagnosis is important for determining the prognosis and conducting genetic counselling of families with cases of the disease.Description of the Clinical Case. The article presents two clinical observations of a severe course of non-compaction cardiomyopathy with remodeling of the heart cavities according to the dilated phenotype. In order to clarify the disease etiology, a molecular genetic study was conducted using the method of direct automatic sequencing with the analysis of targeted regions of 404 genes which mutations are described in hereditary diseases of the heart and blood vessels. After verifying the mutation (in the ACTC1 and MYBPC3 genes), we performed a search for the detected nucleotide substitution in the venous blood samples of parents and in one case — in the fetal DNA sample. The mode of inheritance has been determined; the probability of recurrence of the disease in siblings in subsequent pregnancies has been estimated.Conclusion. The description of clinical cases shows the importance of genetic verification of the diagnosis in patients with non-compaction cardiomyopathy for determining the disease prognosis and developing an algorithm for monitoring relatives of a proband.

scholarly journals GENETIC ASPECTS OF PREGNANCY MISCARRIAGE

2019 ◽  
pp. 71-76
Author(s):  
K. M. Lisova ◽  
I. V. Kalinovska ◽  
O. M. Yuzko
Keyword(s):  
Pregnant Women ◽  
Molecular Genetic ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Control Group ◽  
Molecular Genetic Study ◽  
Immunological Parameters ◽  
Fetoplacental Complex ◽  
Maternal Genotype ◽  
A1166c Polymorphism

Pregnancy miscarriage is a consequence of many factors. The aim of the study was to analyze the effect of miscarriage gene on embryometric, ultrasound, hormonal, immunological parameters in pregnant women, and to evaluate its prognostic value. The main group includes 31 pregnant women who had clinical signs of miscarriage in current or previous pregnancy. The control group consists of 32 healthy pregnant women whose clinical-paraclinical parameters served as a control to compare the data of the pregnancy survey of the main surveillance group. A general clinical examination and a special obstetrical examination (complaints, anamnesis, general medical examination, obstetric examination), biochemical studies (determination of hormones of the fetoplacental complex in blood serum of pregnant women), ultrasound, immunological studies, histological studies of the placenta, molecular genetic study A1166C polymorphism of the AGTR1 gene were made. In the course of the research, the genetic determinism of miscarriage was discovered. The polymorphism of the A1166C of the AGTR1 gene was considered as a prognostic marker of miscarriage in early gestational term and preeclampsia in the second half of pregnancy. A reliable marker of abortion was the maternal genotype 1166AC for the genome AGTR1. The risk of occurrence of clinical manifestations of abortion increased five times. At simultaneous influence of all prognostic factors the risk of abortion increased 6,25 times. Detection of genetic markers of pregnancy miscarriage will allow early correction of this pathology and prevent perinatal loss.

scholarly journals Determination of the carrier frequency of mutations in the CFTR, PAH, GALT and GJB2 genes among 2168 individuals without clinical signs of hereditary diseases

2019 ◽  
pp. 30-35
Author(s):  
Г.Ю. Зобкова ◽  
В.В. Кадочникова ◽  
Д.Д. Абрамов ◽  
А.Е. Донников ◽  
Н.С. Демикова
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Molecular Genetic ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Hereditary Diseases ◽  
Gjb2 Gene ◽  
Frequent Mutations ◽  
High Level ◽  
Autosomal Recessive Diseases

Цель: оценка частоты гетерозиготного носительства мутаций в генах CFTR, PAH, GALT и GJB2 среди здоровых индивидов. Материалы и методы. В исследовании принимали участие 1000 доноров крови, проживающих в Москве и 1168 сотрудников ФГБУ «НМИЦ АГП им. В.И. Кулакова», проживающих в Москве и Московской области. У всех участников исследования отсутствовали клинические проявления наследственных заболеваний. Молекулярно-генетическое исследование образцов проводили путём анализа наиболее частых мутаций в генах CFTR, PAH, GALT и GJB2 с применением технологии real-time PCR Результаты. При генотипировании были выявлены 46 носителей мутаций в гене CFTR, 63 носителя мутаций в гене PAH, 12 носителей мутаций в гене GALT и 74 носителя мутации в гене GJB2. Кроме того, в 3 случаях было установлено сочетанное носительство мутаций: CFTR: F508del + GALT:Q188R; CFTR:dele2,3 (21kb) + GJB2:35delG; GJB2:35delG + GALT:Q188R. Выводы. Полученные данные свидетельствуют о высокой частоте носительства мутаций в исследуемых генах в обследованной выборке. Таким образом, имеются предпосылки для диагностики носительства мутаций, приводящих к наиболее частым аутосомно-рецессивным заболеваниям в популяции. Подобные исследования могут стать эффективным инструментом для профилактики наследственной патологии в семьях носителей мутаций. The study aim was to assess the frequency of heterozygous carriage of mutations in the CFTR, PAH, GALT, and GJB2 genes among healthy individuals. Materials and methods. The study involved 1000 blood donors living in Moscow and 1168 employees of the FSBI Research center for obstetrics gynecology and perinatology MOH Russia, living in Moscow and the Moscow region. All participants in the study did not have clinical manifestations of hereditary diseases. Molecular genetic studies of the samples were carried out by analyzing the most frequent mutations in the CFTR, PAH, GALT and GJB2 genes, using real-time PCR technology Results. 46 carriers of mutations in the CFTR gene, 63 carriers of mutations in the PAH gene, 12 carriers of mutations in the GALT ge ne and 74 carriers of mutations in the GJB2 gene were identified. In addition, in 3 cases, a combined carriage of mutations was found: CFTR: F508del + GALT: Q188R; CFTR: dele2.3 (21kb) + GJB2: 35delG; GJB2: 35delG + GALT: Q188R. Conclusion. The data obtained indicate a fairly high level of carriage of the studied diseases. Thus, there are prerequisites and opportunities for diagnosing the carriage of the most common autosomal recessive diseases in the population. Such studies can be an effective tool for the prevention of hereditary pathologies and reduce the incidence of diseases.

scholarly journals Challenges of the differential diagnosis between the subtypes of the junctional epidermolysis bullosa: presentation of two clinical cases

2019 ◽  
Vol 47 (1) ◽  
pp. 83-93
Author(s):  
Yu. Yu. Kotalevskaya ◽  
N. M. Marycheva
Keyword(s):  
Differential Diagnosis ◽  
Epidermolysis Bullosa ◽  
Skin Disease ◽  
Clinical Case ◽  
Molecular Genetic ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Junctional Epidermolysis Bullosa ◽  
Reliable Determination ◽  
Clinical Cases

Background: Epidermolysis bullosa (EB) is a rare hereditary skin disease. It is subdivided into EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome. JEB is diagnosed in 2 per 1,000,000 of the population. There are few descriptions of clinical JEB cases in the literature. Clinical diagnosis of JEB and its subtypes is a challenge, especially in the early age. The paper presents 2 clinical cases of JEB in patients of the West Slavonic origin. Clinical case No. 1 was a girl of Ukrainian ethnicity, with confirmed definitive diagnosis of severe generalized JEB. Molecular genetic tests identified mutations of the LAMA3 gene that had not been described previously. The patient died at the age of 24 months from acute respiratory failure. When the patient was alive, her EB type and subtype was not possible to identify, because she had a combination of clinical manifestations typical for various JEB subtypes. Despite such symptoms as hoarse voice, stenoses, granulation tissue of typical location, laryngeal granulations, the girl was steadily gaining weight, with some periods of relative stabilization of the skin disease; she also had longer life longevity than was common for patients with severe generalized JEB. All this made a precise diagnosis difficult. Clinical case No. 2: an ethnic Russian boy with non-classified JEB. Molecular genetic testing helped to identify a homozygote mutation in the LAMA3 gene that had not been previously described; reliable determination of the subtype was not possible. The patient had mixed clinical manifestation similar both to generalized severe JEB and to laryngo-onycho-cutaneous (LOC) syndrome. During his lifetime, the patient was clinically diagnosed with Hallopeau acrodermatitis and LOC syndrome. The differential diagnostic problems were associated with the presence of signs not typical for each of the subtypes. Significant life longevity of the proband is not characteristic for severe generalized JEB (at the time of the publication the patient is 13 years old), whereas for LOC syndrome the absence of eye involvement is not typical, as well as severe laryngeal involvement at adolescence.Conclusion: Detailed descriptions of phenotype of JEB subtypes including rare and minimal clinical signs can be useful to study the clinical manifestations and natural course of the disease, including its differential diagnosis.

scholarly journals Pyruvate kinase deficiency: epidemiology, molecular analyses and modern diagnostic approaches (literature review)

2020 ◽  
Vol 7 (2) ◽  
pp. 86-93
Author(s):  
A. V. Bankole ◽  
E. A. Chernyak
Keyword(s):  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Diagnostic Methods ◽  
Compound Heterozygous ◽  
Red Cell ◽  
Molecular Genetic Study ◽  
Pyruvate Kinase Deficiency ◽  
Diagnostic Approaches

Red cell pyruvate kinase deficiency is the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Pyruvate kinase is the enzyme involved in the last step of glycolysis – the transfer of a phosphate group from phosphoenolpyruvate producing the enolate of pyruvate and ATP (50 % of total energy ATP of erythrocytes). ATP deficiency directly shortened red cell lifespan. Affected red blood cells are destroyed in the splenic capillaries, leading to the development of chronic hemolytic anemia. It is an autosomal recessive disease, caused by homozygous and compound heterozygous mutations in the PKLR gene. There are no exact data on the incidence of pyruvate kinase deficiency, but the estimated frequency varies from 3: 1,000,000 to 1:20,000. The clinical features of the disease and the severity are highly variable. Diagnosis of pyruvate kinase deficiency is based on the determination of pyruvate kinase activity and molecular genetic study of the PKLR gene. The variety of clinical manifestations, possible complications, as well as the inaccessibility of diagnostic methods complicate the diagnosis.

scholarly journals PHENOTYPIC CHARACTERISTICS IN OSTEOGENESIS IMPERFECTA PATIENTS

2019 ◽  
Vol 21 (5) ◽  
pp. 266-271
Author(s):  
Olga N. Ignatovich
Keyword(s):  
Osteogenesis Imperfecta ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Clinical Manifestations ◽  
Hereditary Disease ◽  
Type I ◽  
Missense Mutations ◽  
Phenotypic Characteristics ◽  
Molecular Genetic Study ◽  
Collagen Genes

Osteogenesis imperfecta (OI) is a heterogeneous hereditary disease characterized by low bone density and frequent fractures. There are presented data of molecular genetic study and examination of 45 children with a clinically established diagnosis of types I, III and IV. The aim of investigation. To study the variety of clinical manifestations in OI children with and to compare with the identified genetic mutations in the genes COL1A1 and COL1A2. Materials and methods. The data of molecular genetic research and evaluation of clinical manifestations of 45 children with diagnosis OI of types I, III and IV is presented. Results. In the study, mutations in the genes COL1A1 and COL1A2 were detected in 43 (95.6%). The most of the mutations (74,4%) were found to be localized in the gene COL1A1 (n=32), smaller (25.6%) - in the gene COL1A2 (n=11). Glycine-to-serine substitutions in the Gly-X-Y triplet are the most frequent type of mutation among missense mutations. In children with type I qualitative mutations were found to be less common than in types III and IV (representing clinically severe and moderate, respectively). Conclusion. Majority of OI patients had mutations in the collagen genes. The most frequent mutation was the missense mutation, the most often detected in children with OI type III having a severe course, leading to a qualitative violation of collagen.

The echocardiographic aspects of diagnostic of phenomenon of trabecularization of myocardium of left ventricle and non-compact myocardium

2016 ◽  
Vol 22 (1) ◽  
pp. 31-36
Author(s):  
Ol’ga N. Dzhioeva ◽  
E. V Kartashova ◽  
I. I Zakharova ◽  
A. V Melekhov ◽  
G. E Gendlin
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricle ◽  
Diagnostic Criteria ◽  
Transthoracic Echocardiography ◽  
Genetic Disorders ◽  
Systolic Dysfunction ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Main Role

The left ventricular non-compaction is a disease characterizing by hyper-trabecularization of myocardium causing development of chronic heart failure. In the development of structural damages under this pathology the main role belongs to genetic disorders and dysfunction of organogenesis in early periods of gestation. The clinical manifestations are associated with development of systolic dysfunction of left ventricle, intricate abnormalities of rhythm and thromboembolic occurrences. In patients with systolic dysfunction of left ventricle phenomenon of hyper-trabecularization of myocardium is quite often found during transthoracic echocardiography. The modern diagnostic criteria permit approaching differentially issues of verification of non-compact myocardium and redundant trabecularization in patients with chronic heart failure with reduced fraction of output of left ventricle.

Genetic Disorders and Asthma

Asthma ◽  
2014 ◽  
pp. 115-138
Author(s):  
Neetu Talreja ◽  
Ronald Dahl
Keyword(s):  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Hereditary Diseases ◽  
Great Promise ◽  
Diagnostic Strategies ◽  
Antitrypsin Deficiency ◽  
Emerging Treatments ◽  
Important Challenge ◽  
Definition Of

Primary ciliary dyskinesia, cystic fibrosis, and α‎1-antitrypsin deficiency are autosomal recessive hereditary diseases. These diseases should always be considered in cases of asthma. The diagnosis and management of these diseases, particularly with asthma, is an important challenge for clinicians. However, the diagnosis of these chronic diseases is evolving with better definition of phenotypic features and expansion of diagnostic tests. Optimizing and expanding access to the nongenetic tests is critical for ensuring a timely and accurate diagnosis. Early diagnostic strategies, better understanding of the complex interactions underlying the pathophysiology of lung disease, and emerging treatments show great promise for the future. The discovery of genetic and biomarker studies that will predict individuals at risk to develop the clinical manifestations of these diseases can lead to more personalized treatment strategies and a better prognosis.

The non-classical form of congenital adrenal cortical hyperplasia due to 11Β-hydroxylase deficiency: the description of three clinical cases

2013 ◽  
Vol 59 (3) ◽  
pp. 36-44 ◽  
Author(s):  
T A Ionova ◽  
N A Zubkova ◽  
A N Tiul'pakov ◽  
A N Nizhnik ◽  
L V Savel'eva
Keyword(s):  
World Literature ◽  
Molecular Genetic ◽  
Russian Language ◽  
Slight Reduction ◽  
Molecular Genetic Study ◽  
Hydroxylase Deficiency ◽  
Classical Form ◽  
Clinical Conditions ◽  
The Russian Language ◽  
Clinical Cases

The non-classical form of congenital adrenal cortical hyperplasia due to 11Β-hydroxylase deficiency (11Β-OH CAH) is the second most frequent non-classical form of CAH. Mutations in the CYP11B1 gene characteristic of this pathology are responsible for the slight reduction in the 11Β-hydroxylase activity manifested as the "soft" phenotype. They make it difficult to distinguish 11Β-OH CAH from similar clinical conditions. There are occasional publications in the world literature describing patients with genetically confirmed 11Β-OH CAH. No such data can be found in the Russian-language literature. We have described three clinical cases of 11Β-OH CAH caused by mutations in the CYP11B1 gene. Our observations showed that the presence of the signs of hyperandrogenism (regardless of the patients' age and sex) in combination with arterial hypertension or without it as well as the marked increase in the baseline and/or stimulated levels of 11-deoxycortisol gives reason to suspect non-classical variant of 11Β-hydroxylase deficiency. The molecular-genetic study revealed mutations in the CYP11B1 gene in all the examined patients.

Clinical and molecular-genetics diagnosis of microdeletion Xp11.4

2020 ◽  
pp. 35-36
Author(s):  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
Т.В. Маркова ◽  
Н.В. Шилова
Keyword(s):  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Speech Development ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Cerebellar Hypoplasia ◽  
Pontocerebellar Hypoplasia ◽  
Molecular Genetic Study ◽  
Psychomotor Delay ◽  
Study Results

Представлены клинические и молекулярно-генетические результаты обследования девочки с задержкой психомоторного, речевого и физического развития, микроцефалией, гипоплазией моста и мозжечка. Хромосомный микроматричный анализ позволил выявить делецию Хр11.4, затрагивающую ген CASK, который ассоциирован с клиническими проявлениями MICPCH-синдрома (mental retardation and microcephaly with pontine and cerebellar hypoplasia). Сlinical and molecular-genetic study results of a girl with developemental and psychomotor delay, lack of speech development, microcephaly, and pontocerebellar hypoplasia are presented. Chromosomal microarray analysis revealed a deletion of Xp11.4 affecting the CASK gene that is associated with clinical manifestations of MICPCH-syndrome.

scholarly journals KIDNEY TUBULAR ACIDOSIS: CAUSES, SYMPTOMS, DIAGNOSTICS, TREATMENT (LITERATURE DATA AND THE AUTHORS’ OWN OBSERVATIONS)

2020 ◽  
Vol 24 (3-4) ◽  
pp. 33-37
Author(s):  
A.A. Konyushevskaya ◽  
T.A. Parkhomenko ◽  
I.V. Balychevtseva ◽  
I.E. Kramarenko ◽  
V.L. Maliy ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Primary Hyperoxaluria ◽  
Point Of View ◽  
Molecular Genetic Study ◽  
Adequate Treatment ◽  
Initial Symptoms ◽  
Renal Tubular ◽  
Severe Weakness

The article presents a literature review on the etiology, pathogenesis, clinical presentation, diagnosis and therapy of renal tubular acidosis in children, as well as our own 9-years-long observation of a child with this disease. Clinical manifestations from the initial symptoms starting at 3.5 years of age in the form of recurrent acetonemic states, episodes of dehydration with fever, and polyuria were analyzed. Further dynamics of symptoms was traced in the form of severe weakness in the legs, rapid fatigue, gait disturbance, inability to running, jumping, X-shaped deformity of the lower extremities. The literature data on the erroneous prescription of massage to a child with rickets-like diseases without normalization of phosphorus-calcium metabolism and disappearance of acidosis signs are presented. A thorough analysis of these mistakes was carried out and the positive dynamics was demonstrated in the clinical condition and development of the child in response to adequate treatment after a correctly made diagnosis. The differential diagnosis was carried out with Fanconi's syndrome, proximal RTA, hyperparathyroidism, primary hyperoxaluria. Molecular genetic study permitted to exclude cystinosis. Such children require constant monitoring and treatment by specialists, primarily from the point of view of preventing the renal failure progression. Knowledge of the features of renal tubular acidosis course will significantly help the clinicians in making the diagnosis, prescribing consultations of narrow specialists, as well as choosing an adequate treatment tactics.

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