scholarly journals Congenital hyperinsulinism. Results of molecular-genetic investigations in a Russian population

2012 ◽  
Vol 58 (2) ◽  
pp. 3-9 ◽  
Author(s):  
M A Melikian ◽  
M A Kareva ◽  
E E Petriaĭkina ◽  
I É Volkov ◽  
Iu V Aver'ianova ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Clinical Manifestations ◽  
First Year ◽  
Congenital Hyperinsulinism ◽  
Heterogeneous Condition ◽  
Histological Features ◽  
Pancreatic Cells ◽  
Genes Encoding ◽  
First Year Of Life ◽  
Intracellular Glucose

Congenital hyperinsulinism (CHI) is a most frequent cause of persistent hypoglycemia in the children during the first year of life. This pathology is biochemically characterized by inadequate secretion of insulin by beta-cells of the pancreas. Congenital hyperinsulinism is a highly heterogeneous condition in terms of clinical manifestations, histological features, and molecular-genetic defects underlying the development of this disorder. A total of 9 genes are known to be involved in pathogenesis of CHI. The majority of the cases (40-60%) are attributable to the defects in KCNJ11 and ABCC8 genes encoding for the ATP-dependent potassium channels in the pancreatic cells. Approximately 15-20% cases are associated with the mutations of GCK and GLUD1 genes participating in the regulation of intracellular glucose metabolism. The results of clinical, hormonal, molecular-genetic, and histological examination of 42 children presenting with congenital hyperinsulinism are reported. These data were used to analyse the genotype-phenotype relationships.

scholarly journals Dravet syndrome associated mutations in GABRA1, GABRB2 and GABRG2 define the genetic landscape of defects of GABAA receptors

2021 ◽  
Author(s):  
Ciria C Hernandez ◽  
XiaoJuan Tian ◽  
Ningning Hu ◽  
Wangzhen Shen ◽  
Mackenzie A Catron ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Dravet Syndrome ◽  
First Year ◽  
Genes Encoding ◽  
Genetic Landscape ◽  
Clonic Seizures ◽  
Trafficking Defects ◽  
First Year Of Life

Abstract Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. De novo variants in genes that mediate synaptic transmission such as SCN1A and PCDH19 are often associated with Dravet syndrome. Recently, GABAA receptor subunit genes (GABRs) encoding α1 (GABRA1), β3 (GABRB3) and γ2 (GABRG2), but not β2 (GABRB2) or β1 (GABRB1), subunits are frequently associated with Dravet syndrome or Dravet syndrome-like phenotype. We performed next generation sequencing on 870 patients with Dravet syndrome and identified nine variants in three different GABRs. Interestingly, the variants were all in genes encoding the most common GABAA receptor, the α1β2γ2 receptor. Mutations in GABRA1 (c.644T>C, p.L215P; c.640C>T, p.R214C; c.859G>A; V287I; c.641G>A, p.R214H) and GABRG2 (c.269C>G, p.T90R; c.1025C>T, p.P342L) presented as de novo cases, while in GABRB2 two variants were de novo (c.992T>C, p.F331S; c.542A>T, p.Y181F) and one was autosomal dominant and inherited from the maternal side (c.990_992del, p.330_331del). We characterized the effects of these GABR variants on GABAA receptor biogenesis and channel function. We found that defects in receptor gating were the common deficiency of GABRA1 and GABRB2 Dravet syndrome variants, while mainly trafficking defects were found with the GABRG2 (c.269C>G, p.T90R) variant. It seems that variants in α1 and β2 subunits are less tolerated than in γ2 subunits, since variant α1 and β2 subunits express well but were functionally deficient. This suggests that all of these GABR variants are all targeting GABR genes that encode the assembled α1β2γ2 receptor, and regardless of which of the three subunits are mutated, variants in genes coding for α1, β2 and γ2 receptor subunits make them candidate causative genes in the pathogenesis of Dravet syndrome.

scholarly journals Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 523
Author(s):  
Rosa Estela Gazeta ◽  
Ana Paula Antunes Pascalicchio Bertozzi ◽  
Rita de Cássia de Aguirre Bernardes Dezena ◽  
Andrea Cristina Botelho Silva ◽  
Thamirys Cosmo Gillo Fajardo ◽  
...  
Keyword(s):  
Zika Virus ◽  
Clinical Manifestations ◽  
Laboratory Diagnosis ◽  
Autism Spectrum ◽  
First Year ◽  
Cognitive Delay ◽  
Long Term Follow Up ◽  
Simplex Virus ◽  
First Year Of Life

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

Investigation of the possible effectiveness of osteopathic correction in the complex treatment of children in the first year of life with hip dysplasia

2021 ◽  
pp. 39-49
Author(s):  
N. A. Fabristova ◽  
I. R. Gainullin
Keyword(s):  
Hip Dysplasia ◽  
Standard Treatment ◽  
Clinical Manifestations ◽  
Standards Of Care ◽  
First Year ◽  
Complex Treatment ◽  
Hip Joints ◽  
Congenital Diseases ◽  
Detection Frequency ◽  
First Year Of Life

Introduction. Congenital dysplasia of the hip joints is one of the main among congenital diseases of the musculoskeletal system in children and requires a long period of treatment, including in a hospital settings. Standard methods of treatment contain the orthopedic and rehabilitation measures: the use of abduction splints, a complex of physiotherapy exercises, general massage, the use of various physiotherapeutic procedures. Osteopathic correction is not included in the standards of care for this category of patients. At the same time, these standard treatment methods do not always give a desired result, and sometimes even lead to the development of complications. All this facts determines the need to search for additional therapeutic techniques.The aim of the study is to research the possible effectiveness of osteopathic correction as part of the complex treatment of children in the first year of life with hip dysplasia.Materials and methods. The study included 34 children with a diagnosis of hip dysplasia (ICD code-10 — Q65.8). The patients were randomly divided into 2 equivalent groups: study and control. Participants in both groups received standard treatment; the participants of the main group additionally underwent osteopathic correction of the revealed somatic dysfunctions. Before and after the course of treatment, the patients' osteopathic status, the disease clinical manifestations, and the X-ray data of the hip joints were assessed.Results. The inclusion of osteopathic correction in the complex with standard treatment procedures for children of the first year of life with hip dysplasia is accompanied by a statistically significant decrease in the detection frequency of the somatic dysfunctions at the regional and local levels. The median duration of standard orthopedic treatment also decreases (p<0,05).Conclusion. The obtained results demonstrate that the inclusion of osteopathic correction in the complex treatment of children in the first year of life with hip dysplasia shortens the treatment time for patients. It is recommended to continue research in this direction with a larger sample size.

scholarly journals Incidental Finding of MEGDEL Syndrome Based on Neuroimaging: Case Report

2021 ◽  
pp. 429-433
Author(s):  
Salma A. Alshammari ◽  
Fouad A. Alghamdi ◽  
Rami Alhazmi ◽  
Shaikhah Aldossary
Keyword(s):  
Incidental Finding ◽  
Molecular Genetic ◽  
Cerebellar Atrophy ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Disease Diagnosis ◽  
First Year ◽  
Pathogenic Variants ◽  
Clinical Presentations ◽  
First Year Of Life

MEGDEL 3-methylglutaconic (MG) aciduria, deafness, encephalopathy, Leigh-like syndrome is an autosomal recessive disorder associated with infantile hypoglycemia, progressive psychomotor developmental delay, cerebellar atrophy with lesions in the basal ganglia, spasticity, dystonia, deafness, and transient liver problems, which typically occur in the first year of life. Other clinical presentations include failure to thrive, epilepsy, and optic nerve atrophy. The serine active site-containing 1 (SERAC1) mutation is localized at the mitochondria-associated membranes, which are responsible for encoding a phosphatidylglycerol remodeler essential for both mitochondrial function and intracellular cholesterol trafficking and is thus responsible for the disease. Diagnosis is confirmed by the elevation of and concentrations of 3-MG acid and 3-methylglutaric acid in the urine or by identification of bi-allelic SERAC1 pathogenic variants on molecular genetic testing. Different pathological variants of SERAC1 have been identified in MEGDEL syndrome to date. Here, we report a case of a child with MEGDEL syndrome due to SERAC1 mutation. The child presented with accidental finding by CT showing hypodensity on bilateral symmetric anterior putamen and caudate abnormal. Neurological examination was unremarkable. This report presents a new neuroimaging finding by CT of MEGDEL syndrome.

scholarly journals Molecular genetic study of clinical and cognitive features of schizophrenia: No associations with genes SOD2, GSTO1, NQO1

2022 ◽  
Vol 36 (4) ◽  
pp. 99-106
Author(s):  
E. G. Poltavskaya ◽  
O. Yu. Fedorenko ◽  
E. G. Kornetova ◽  
S. A. Ivanova
Keyword(s):  
Antioxidant Enzymes ◽  
Cognitive Abilities ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Russian Population ◽  
Healthy Individuals ◽  
Siberian Region ◽  
Genes Encoding ◽  
Schizophrenic Patients ◽  
Polymorphic Variants

 The main features of schizophrenia are characterized by three domains of symptoms, including positive symptoms, negative symptoms, and cognitive defi cits, the overlap of which forms a polymorphism of clinical manifestations. Previous molecular genetic studies have found signifi cant genetic overlaps between the cognitive abilities and the risk of schizophrenia developing. Recent evidence suggests that oxidative stress may play an important role in the pathophysiology of schizophrenia.Aim. The aim of the study was to investigate the associations of polymorphisms of genes encoding the antioxidant enzymes SOD2, GSTO1, and NQO1 with clinical polymorphism of schizophrenia and the severity of cognitive deficit.Material and Methods. A comprehensive examination of 457 patients with a diagnosis of schizophrenia was carried out. Out of the total group of examined patients, cognitive functions were assessed using the BACS scale in 150 schizophrenic patients. The control group comprised 135 healthy individuals with age and gender corresponding to patient group. Their cognitive function was assessed. Genotyping of SOD2 (rs4880), GSTO1 (rs4925), and NQO1 (rs1800566) was done by realtime PCR.Results. When analyzing the distribution of genotypes and alleles of polymorphic variants of genes encoding the antioxidant enzymes SOD2, GSTO1, and NQO1, no associations between the studied loci and schizophrenia in the Russian population of the Siberian region were revealed. Also, no associations were found with clinical polymorphism of disease (disease course type, leading symptoms (positive or negative), and age of disease onset). The cognitive abilities of schizophrenic patients and healthy individuals were diff erent as expected, but no associations with genetic characteristics were found.Conclusion. In this work, we obtained negative results in regard to associations of polymorphic variants of genes encoding the antioxidant enzymes SOD2 (rs4880), GSTO1 (rs4925), and NQO1 (rs1800566) with the development of schizophrenia in the Russian population in the Siberian region, as well as with the severity of cognitive defi cit. The genetic profi le for the studied loci did not aff ect the clinical manifestations of disease in the examined sample.

scholarly journals Neonatal Diabetes Mellitus in the Structure of IPEX Syndrome

2017 ◽  
Vol 8 (2) ◽  
pp. 99-104
Author(s):  
Mariia E Turkunova ◽  
Liliya V Ditkovskaya ◽  
Evgenii N Suspitsin ◽  
Ludmila V Tyrtova ◽  
Ludmila A Jelenina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Manifestations ◽  
Neonatal Diabetes ◽  
Skin Lesions ◽  
Neonatal Diabetes Mellitus ◽  
First Year ◽  
Permanent Neonatal Diabetes ◽  
Severity Of The Disease ◽  
Clinical Triad ◽  
First Year Of Life

This disease is characterized by the onset of primary immunodeficiency, which expresses itself as autoimmune multisystem failure, often clinically manifests during the first year of life; there are only about 150 cases in the world described by now. IPEX syndrome is caused by FOXP3 gene defect, which is a transcription factor that affects the activity of regulatory T-cells responsible for the maintenance of aytotolerance. There are around 70 pathogenic mutations in this gene described so far. Most patients with IPEX-syndrome have a clinical manifestations of the disease in the early neonatal period or during the first 3-4 months of life. For this disease the following clinical triad of manifestations is typical: Autoimmune enteropathy (100%), diabetes mellitus (70%), skin lesions (65%), as in the syndrome structure includes severe developmental delay (50%), thyroid disease (30%), recurrent infections (20%), rarer autoimmune cytopenia (Coombs-positive hemolytic anemia), pneumonia, nephritis, hepatitis, artrit, myositis, alopecia. However, some cases of later manifestations were described (in patients of more than 1 year of age) when patients did not show all clinical and laboratory symptoms typical for severe forms of the disease. Due to the severity of the disease and the high mortality in this group of patients, it is very important to diagnose it early and start therapy timely. The article describes a clinical case of permanent neonatal diabetes mellitus in the structure of IPEX syndrome.

scholarly journals POLR3A-related hypomyelinating leukodystrophy: case report and literature review

2020 ◽  
Vol 11 (4) ◽  
pp. 48-54
Author(s):  
A. F. Murtazina ◽  
T. V. Markova ◽  
A. A. Orlova ◽  
O. P. Ryzhkova ◽  
O. A. Shchagina ◽  
...  
Keyword(s):  
Case Report ◽  
Hypogonadotropic Hypogonadism ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Permanent Teeth ◽  
Diagnostic Process ◽  
Compound Heterozygous ◽  
Compound Heterozygous Variants ◽  
First Year Of Life

Hypomyelinating leukodystrophies (HL) is a group of genetically heterogeneous neurodegenerative disorders characterized by a lack of brain myelin deposition. One of the most common autosomal recessive HL is HL type 7 caused by mutations in the POLR3A gene. We reported the first clinical case of a Russian patient with HL type 7.Proband is a 7‑year‑old patient with HL type 7. The diagnosis was confirmed by genealogy, neurological examination, brain magnetic resonance imaging and molecular genetic testing. Two compound‑heterozygous variants in the POLR3A gene were revealed in the patient. Each variant was described earlier in patients with variable clinical manifestations of neurodegenerative diseases. The peculiarities of clinical manifestations in our patient were the manifestation of the disease in the first year of life, the predominance of cerebellar symptoms, a movement limitation of the jaw, leading to worsening of dysarthria, a delay in the formation of permanent teeth and short stature. The course of the disease was moderate that could be explained by different effect of the variants in the POLR3A gene.POLR3A‑related disease is a group of clinically heterogeneous disorders manifesting from early childhood to adulthood and characterized by isolated spastic ataxia or ataxia combined with oligodontia and hypogonadotropic hypogonadism, isolated or complicated spastic paraplegia, as well as a combination of ataxia with extrapyramidal symptoms. Our case report demonstrates the complexity of diagnostic process in the absence of a peculiar clinical picture and specific changes in brain imaging.

scholarly journals Molecular-genetic characteristics of strain Escherichia coli serogroup O26 causing diarrheal diseases in children

2018 ◽  
Vol 18 (3) ◽  
pp. 85-90
Author(s):  
M A Makarova ◽  
A V Dmitriev ◽  
Z N Matveeva ◽  
K A Kaftyreva
Keyword(s):  
Virulence Genes ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Phylogenetic Group ◽  
Intestinal Infection ◽  
Genetic Characteristics ◽  
E Coli ◽  
Saint Petersburg ◽  
Antigenic Properties ◽  
Genes Encoding

Aim. To determine the serotype and virulence factors of the E. coli serogroup O26 isolated from children with diarrheal syndrome. Materials and methods. Fifty-three strains of E. coli O26 isolated in 2014-2016 from the stool of children with clinical manifestations of acute intestinal infection in Saint Petersburg were studied. Phenotypic (enzymatic and antigenic properties), molecular genetic [detection of virulence genes of enteropathogenic (EPEC - eae, bfp, hlyA), and enterohemorrhagic (EHEC - eae, stx1, stx2, ehxA), genes encoding O- and H-antigens (rfb and fliC), genes, defining phylogenetic group (chuA, yjaA и TspE)] methods were used. The phylogenetic group and the production Shiga toxins were determined. Results. All strains were identical to the antigen characteristics of serotype O26:H11 and phylogenetic group B1. Two pathogroups were created based on the set of virulence genes: a-EPEC (64.2%) and EHEC (35.8%). Strains EHEC produced Shiga-toxin 1, encoding gen stx1. No differences in enzymatic activities were found between the strains of E. coli О26:H11 for EPEC and EHEC strains. Conclusion. In the population of E. coli O26:H11, which caused acute intestinal infection in children in Saint Petersburg, more than 30% of the strains belonged to the highly virulent group EHEC. Molecular-genetic methods should be used for reliable detection of pathogens.

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