scholarly journals Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3117
Author(s):  
Nobuhiko Okamoto ◽  
Tatsuyuki Ohto ◽  
Takashi Enokizono ◽  
Yoshinao Wada ◽  
Tomohiro Kohmoto ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Metabolic Diseases ◽  
Clinical Manifestations ◽  
Epileptic Encephalopathy ◽  
Whole Exome ◽  
Microsome Fraction ◽  
Biochemical Profiles ◽  
Processing Defects ◽  
Characteristic Features

Congenital disorders of glycosylation (CDG), inherited metabolic diseases caused by defects in glycosylation, are characterized by a high frequency of intellectual disability (ID) and various clinical manifestations. Two siblings with ID, dysmorphic features, and epilepsy were examined using mass spectrometry of serum transferrin, which revealed a CDG type 2 pattern. Whole-exome sequencing showed that both patients were homozygous for a novel pathogenic variant of MAN1B1 (NM_016219.4:c.1837del) inherited from their healthy parents. We conducted a HPLC analysis of sialylated N-linked glycans released from total plasma proteins and characterized the α1,2-mannosidase I activity of the lymphocyte microsome fraction. The accumulation of monosialoglycans was observed in MAN1B1-deficient patients, indicating N-glycan-processing defects. The enzymatic activity of MAN1B1 was compromised in patient-derived lymphocytes. The present patients exhibited unique manifestations including early-onset epileptic encephalopathy and cerebral infarction. They also showed coagulation abnormalities and hypertransaminasemia. Neither sibling had truncal obesity, which is one of the characteristic features of MAN1B1-CDG.

scholarly journals Genetic epilepsy caused by CDKL5 gene mutations as an example of epileptic encephalopathy and developmental encephalopathy: literature review and own observations

2021 ◽  
Vol 16 (1-2) ◽  
pp. 10-41
Author(s):  
K. Yu. Mukhin ◽  
O. A. Pylaeva ◽  
M. Yu. Bobylova ◽  
V. A. Chadaev
Keyword(s):  
Literature Review ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Case Series ◽  
Gene Mutations ◽  
Epileptic Encephalopathy ◽  
Serine Threonine Kinase ◽  
Gene Encoding ◽  
Threonine Kinase

The disease caused by mutations in the CDKL5 gene (encoding cyclin-dependent kinase 5, CDK5) belongs to the group of early (infantile) epileptic encephalopathies caused by alterations in the genome. Currently, the disease is called “developmental encephalopathy and epileptic encephalopathy type 2”. This disorder is a complex combination of symptoms that develop due to deficiency or absence of the CDKL5 gene product, which is serine/threonine kinase. The CDKL5 gene is located on X chromosome; the disease has an X-linked dominant inheritance pattern. This literature review summarizes relevant studies analyzing the disease caused by CDKL5 gene mutations, including its genetic and epidemiological aspects, clinical manifestations, characteristics of epilepsy, principles of diagnosis, and therapeutic approaches. We present a case series of several patients with genetic disorders involving the CDKL5 gene.

scholarly journals Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

2020 ◽  
Vol 14 (3) ◽  
pp. 28-36
Author(s):  
E. L. Dadali ◽  
I. A. Akimova ◽  
F. A. Konovalov ◽  
P. A. Shatalov ◽  
A. Yu. Krasnenko ◽  
...  
Keyword(s):  
Genetic Variant ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Psychomotor Retardation ◽  
Dominant Inheritance ◽  
Common Genetic Variant ◽  
Genetic Characteristics

Early infantile epileptic encephalopathies (EIEE) are a group of disorders characterized by pharmacoresistant epileptic seizures manifesting in infancy and leading to psychomotor retardation. The most common genetic variant with X-linked dominant inheritance is type 2 EIEE associated with CDKL5 gene mutations. We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE. The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.

Mutations of mtDNA in some vascular and metabolic diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Anastasia I. Ryzhkova ◽  
Vasily V. Sinyov ◽  
Marina D. Sazonova ◽  
Tatiana V. Kirichenko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Chronic Diseases ◽  
Metabolic Diseases ◽  
Present Review ◽  
Mtdna Mutations

Background: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and as a result, death.In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies and type 2 diabetes mellitus. Objective: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis, Results: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension and various types of cardiomyopathies. Conclusion: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for treatment of these pathologies. MtDNA mutations associated withthe absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of diseases of vascular and metabolic genesis.

scholarly journals Facial cleft? The first case of manitoba‐oculo‐tricho‐anal syndrome with novel mutations in China: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuchen Gu ◽  
Yimin Khoong ◽  
Xin Huang ◽  
Tao Zan
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestations ◽  
Sporadic Case ◽  
Facial Cleft ◽  
Ocular Manifestations ◽  
First Case ◽  
Whole Exome ◽  
Chinese Girl ◽  
Low Prevalence

Abstract Background Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare syndrome with only 27 cases reported worldwide so far, but none was reported in the population of Eastern Asia. Such extremely low prevalence might be contributed by misdiagnosis due to its similarities in ocular manifestations with facial cleft. In our study, we discovered the first case of MOTA syndrome in the population of China, with 2 novel FRAS1 related extracellular matrix 1 (FREM1) gene stop-gain mutations confirmed by whole exome sequencing. Case presentation A 12-year-old Chinese girl presented with facial cleft-like deformities including aberrant hairline, blepharon-coloboma and broad bifid nose since birth. Whole exome sequencing resulted in the identification of 2 novel stop-gain mutations in the FREM1 gene. Diagnosis of MOTA syndrome was then established. Conclusions We discovered the first sporadic case of MOTA syndrome according to clinical manifestations and genetic etiology in the Chinese population. We have identified 2 novel stop-gain mutations in FREM1 gene which further expands the spectrum of mutational seen in the MOTA syndrome. Further research should be conducted for better understanding of its mechanism, establishment of an accurate diagnosis, and eventually the exploitation of a more effective and comprehensive therapeutic intervention for MOTA syndrome.

Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation

2015 ◽  
Vol 129 (12) ◽  
pp. 1083-1096 ◽  
Author(s):  
Joseph B. McPhee ◽  
Jonathan D. Schertzer
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
The Body ◽  
Tissue Inflammation ◽  
Gut Barrier Function ◽  
Inflammatory Status ◽  
Obesity And Diabetes

The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

scholarly journals Spontaneous Type 2 Diabetic Rodent Models

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-wei Wang ◽  
Guang-dong Sun ◽  
Jing Sun ◽  
Shu-jun Liu ◽  
Ji Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Health Care ◽  
Animal Models ◽  
Rodent Models ◽  
Advantages And Disadvantages ◽  
Characteristic Features ◽  
Type 2 Diabetic

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

Intramyocellular fat storage in metabolic diseases

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Claire Laurens ◽  
Cedric Moro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Recent Literature ◽  
Lipid Storage ◽  
Muscle Lipid ◽  
The Past ◽  
Skeletal Muscle Lipid ◽  
Ectopic Lipid Storage

AbstractOver the past decades, obesity and its metabolic co-morbidities such as type 2 diabetes (T2D) developed to reach an endemic scale. However, the mechanisms leading to the development of T2D are still poorly understood. One main predictor for T2D seems to be lipid accumulation in “non-adipose” tissues, best known as ectopic lipid storage. A growing body of data suggests that these lipids may play a role in impairing insulin action in metabolic tissues, such as liver and skeletal muscle. This review aims to discuss recent literature linking ectopic lipid storage and insulin resistance, with emphasis on lipid deposition in skeletal muscle. The link between skeletal muscle lipid content and insulin sensitivity, as well as the mechanisms of lipid-induced insulin resistance and potential therapeutic strategies to alleviate lipotoxic lipid pressure in skeletal muscle will be discussed.

Clinical and pathogenetic features of intestinal lesions in patients with type 2 diabetes mellitus

2021 ◽  
Author(s):  
Y. Z. Dynia
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Clinical Manifestations ◽  
Intestinal Damage ◽  
Hydrogen Breath Test

Objective — to study the incidence and clinical and pathogenetic features of intestinal injury in patients with type 2 diabetes mellitus. Materials and methods. Examinations involved 138 patients with type 2 diabetes mellitus (DM 2), aged from 39 to 67 years (mean age 53 ± 5 years), including 82 women (59 %) and 56 men (41 %). In addition to general clinical methods, investigations included plasma levels of the transforming growth factor‑b1 (TGF‑b1) and vascular endothelial growth factor (VEGF), the hydrogen breath test with lactulose, endoscopic examination of the intestine with biopsy followed by staining with hematoxylin‑eosin, immunohistochemical determining of claudin‑1 and VEGF, and conduction of PAS‑reaction. Results. Diabetic enterocolopathy (DECP) was diagnosed in 72 (52.2 %) patients with DM 2. Clinical manifestations were nonspecific and similar to those of irritable bowel syndrome (IBS). It has been found that DECP correlates with the duration of the DM 2 course and was diagnosed more often in middle‑aged patients (52.1 ± 4.1 years). In patients with DECP, the increase in the proinflammatory cytokines TGF‑b1 and VEGF significantly exceeded those in IBS patients. Histologically the inflammatory cell infiltration in patients with DECP was more intense and diverse, there were signs of subatrophy of the glands with a relative decrease in the number of vacuoles in the goblet cells. The immunohistochemical study revealed that VEGF in the colon mucosa was visualized mainly in patients with DECP. Moreover, a tendency to a decrease in the claudin‑1 levels was established in these patients. Conclusions. Intestinal damage was revealed in 67.4 % of patients with type 2 diabetes mellitus, and DECP was diagnosed in more than half of patients. Diabetic enterocolopathy had nonspecific clinical symptoms, required differential diagnosis with IBS, and was not always accompanied with abdominal pain. The presence of DECP more often correlated with the bacterial overgrowth syndrome, and levels of proinflammatory cytokines in the blood plasma and intestinal mucosa of these patients was raised.  

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