scholarly journals Combination of lipoatrophic diabetes mellitus with systemic scleroderma and phenylketonuria

2017 ◽  
Vol 63 (2) ◽  
pp. 130-133
Author(s):  
Galina N. Svetlova ◽  
Tamara L. Kuraeva ◽  
Dmitriy L. Alekseev ◽  
Valentina A. Peterkova
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Molecular Genetic Analysis ◽  
Systemic Scleroderma ◽  
Dietary Regimen ◽  
Insulin Resistant ◽  
Lipoatrophic Diabetes ◽  
Liver Functions ◽  
High Doses

We present the first report of a rare form of lipoatrophic diabetes mellitus in a child with partial autoimmune lipodystrophy combined with systemic scleroderma and phenylketonuria. We describe the features of clinical manifestations, diagnosis, and therapy. To exclude the monogenic form of lipodystrophy, we performed a molecular genetic analysis of genes ZMPSTE24, LMNA, BSCL2, PLIN1, PTRF, LMNB2, POLD1, AKT2, CIDEC, PIK3CA, PPARG, PSMB8, CAV1, PPP1R3A, and AGPAT2 that are responsible for the development of lipodystrophy and insulin resistance. No mutations were found. The presence of systemic scleroderma of autoimmune genesis enabled the diagnosis of autoimmune lipodystrophy. Treatment of insulin-resistant diabetes mellitus in lipodystrophy is a challenge: biguanide therapy is dangerous due to impairment of liver functions, and insulin therapy is not effective enough; administration of high doses is required. The presence of phenylketonuria further complicates compliance with the dietary regimen. The combination of three rare diseases ― lipoatrophic diabetes, phenylketonuria, and systemic scleroderma ― in one patient has not been found in the available literature.

scholarly journals Molecular-genetic, immunological bases and prophylaxis of diabetes mellitus in children

2011 ◽  
Vol 57 (1) ◽  
pp. 9-18
Author(s):  
E V Titovich
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Russian Population ◽  
Research Centre ◽  
Diabetic Patients ◽  
Genetic Studies

Since the autoimmune nature of type 1 diabetes mellitus came to become known some 40 years ago, continuous investigations have been carried out in an attempt to improve approaches to prognostication of this disease and develop new safe and efficacious methods for its prevention. For all that, many aspects of diabetes pathogenesis still remain far from clear. In most cases (roughly 85%), type 1 diabetes mellitus (DM1) develops sporadically in the absence of a relevant familial or hereditary history of this condition. Accordingly, the first-degree relatives account for only 15% of all DM1 patients. The risk of development of DM1 in the Russian population estimated by the researchers of the Children' Department, Endocrinological Research Centre, is relatively low (0.2%). It depends on many factors, such as the number of ill and healthy relatives, the chronological age of a given patient and the age of onset of clinical manifestations in his (her) relatives. Type 1 diabetes-predisposing and protective haplotypes were identified in the Russian population based on the results of molecular-genetic studies involving 599 children and adolescents with DM1. These and immunological data were used to distinguish between risk groups in the families of diabetic patients and the rationale was proposed for the dynamic follow-up of these subjects. It is concluded that estimation of the risk of type 1 diabetes mellitus based on the results of molecular-genetic studies and monitoring immunological markers constitutes the first step in the elaboration of preventive measures designed to prevent or delay the development of the disease.

POLYMORPHISM OF GENE IL2-330Т>>G AND EXPRESSION OF INTERLEUKIN-2 IN PATIENTS WITH VENOUS THROMBOEMBOLIC COMPLICATIONS OF POLYTRAUMA

2017 ◽  
Author(s):  
А. Мироманов ◽  
В. Доржеев ◽  
Н. Мироманова ◽  
Ю. Витковский
Keyword(s):  
Molecular Genetic ◽  
Interleukin 2 ◽  
Clinical Manifestations ◽  
Molecular Genetic Analysis ◽  
Control Group ◽  
Thromboembolic Complications ◽  
Inclusion Criteria ◽  
Study Results ◽  
Venous Thromboembolic ◽  
Analysis Point

Введение. Политравма отличается особой тяжестью клинических проявлений, сопровождается значительным нарушением жизненно важных функций организма, трудностью диагностики и лечения, частым развитием разнообразных осложнений, длительным периодом пребывания в стационаре и высокой инвалидизацией. Тромбоэмболические осложнения при политравме встречаются в 40–77% случаев и характеризуются скрытым клиническим течением, трудностью лечения и высокой летальностью. Цель исследования. Изучить влияние полиморфизма гена IL2-330T{>{G на экспрессию интерлейкина-2 (IL-2) у пациентов с венозными тромбоэмболическими осложнениями (ВТЭО) политравмы в Забайкальском крае. Материалы и методы. В исследование включено 114 пациентов (71,9% мужчин и 28,1% женщин) в возрасте от 20 до 40 лет с политравмой. Критерий включения в исследование: политравма с индексом по шкале ISS более 9. Первая группа — 73 пациента с неосложнённым течением политравмы, вторая группа — 41 пациент с ВТЭО политравмы. Контрольную группу составили 100 практически здоровых мужчин и женщин в возрасте от 20 до 40 лет. Материалом для молекулярно-генетического анализа служили образцы ДНК, выделенные из периферической крови. Для исследования выбрана точковая мутация IL-2 в позиции 330 (Т{>{G). Результаты. У пациентов с ВТЭО политравмы регистрировали более частое носительство генотипа -330T/T гена IL2; наличие этого генотипа сопровождалось увеличением продукции IL-2. Заключение. Идентификация генов и раскрытие их влияния на экспрессию кодируемых молекул способствует более глубокому пониманию патогенетических механизмов развития осложнений. Introduction. Polytrauma is characterized by a specifi c severity of clinical manifestations, is accompanied by a signifi cant impairment of vital body functions, the diffi culty of diagnosis and treatment, frequent development of various complications, prolonged period of hospitalization and high disability. Thromboembolic complications of polytrauma occur in 40–77% of cases and characterized by latent clinical course, diffi culties in treatment and high mortality. The aim was to study the eff ect of gene IL2-330T{>{G polymorphism on the expression of interleukin-2 (IL-2) at patients with venous thromboembolic complications (VTE) of polytrauma in Zabaykalskiy Krai. Materials and methods. The study included 114 patients (71,9% men and 28,1% women) with polytrauma aged from 20 to 40 years. Inclusion criteria: polytrauma with index according ISS scale more than 9. First group — 73 patients with uncomplicated polytrauma, second group — 41 patients with VTE of polytrauma. Control group consisted of 100 practically healthy men and women aged from 20 to 40 years. DNA samples isolated from the peripheral blood were the material for molecular genetic analysis. Point mutation of IL-2 at position 330 (T{>{G) was selected for study. Results. Genotype -330T/T of IL2 gene was registered more frequently at patients with VTE of polytrauma; the presence of this genotype was accompanied by increased production of IL-2. Conclusion. Identifi cation of genes and their eff ects on the expression of encoded molecules assists more overall understanding of pathogenetic mechanisms of complications development.

Marfan Syndrome

2005 ◽  
Vol 44 (04) ◽  
pp. 487-497 ◽  
Author(s):  
G. Mátyás ◽  
B. Steinmann ◽  
D. Baumgartner ◽  
C. Baumgartner
Keyword(s):  
Medical Treatment ◽  
Marfan Syndrome ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Hierarchical Cluster ◽  
Molecular Genetic Analysis ◽  
Missense Mutations ◽  
Surgical Interventions

Summary Objectives: Marfan syndrome (MFS) is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene with variable clinical manifestations in the cardiovascular, musculoskeletal and ocular systems. Methods: Data of molecular genetic analysis and a catalogue of clinical manifestations including aortic elastic parameters were mined in order to (i) assess aortic abnormality before and during medical treatment, and to (ii) identify novel correlations between the genotype and phenotype of the disease using hierarchical cluster analysis and logistic regression analysis. A score measure describing the similarity between a patient’s clinical symptoms and a characteristic phenotype class was introduced. Results: A probabilistic model for monitoring the loss of aortic elasticity was built on merely aortic parameters of 34 patients with classic MFS and 43 control subjects showing a sensitivity of 82% and a specificity of 96%. The clinical phenotypes of 100 individuals with classical or suspected MFS were clustered yielding four different phenotypic expressions. The highest correlation was found between FBN1 missense mutations, which manifested as ectopia lentis, skeletal major and skin minor criteria, and two out of four clustered phenotypes. The probability of the presence of a missense mutation in both phenotype classes is approximately 70%. Conclusions: Monitoring of aortic elastic properties during medical treatment may serve as additional criterion to indicate elective surgical interventions. Genotype-phenotype correlation may contribute to anticipate the clinical consequences of specific FBN1 mutations more comprehensively and may be helpful to identify MFS patients at risk at an early stage of disease.

MODY3 in the children and adolescents: the molecular-genetic basis and clinico-laboratory manifestations

2015 ◽  
Vol 61 (3) ◽  
pp. 16-22 ◽  
Author(s):  
E A Sechko ◽  
T L Kuraeva ◽  
L I Zil’berman ◽  
O N Ivanova ◽  
V A Peterkova
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Molecular Genetic ◽  
Fasting Blood Glucose ◽  
Clinical Manifestations ◽  
Common Mutation ◽  
Molecular Genetic Basis ◽  
Diabetes Mellitus Diagnosis ◽  
History Of ◽  
Hba1c Levels

The present study of HNF1А gene involved 121 children suspected to have the nonimmune-mediated form of diabetes mellitus. Diagnosis of MODY3 was verified in 18 (19.4%) probands. Disturbances of carbohydrate metabolism in one of the parents were documented in 94.5% of the cases. Metabolic disorders were revealed in the probands at the mean age of 11.65 years (9.8; 14.6), the clinical manifestations of diabetes mellitus (DM) were apparent in 16.7% of the children, the fasting blood glucose level was 7.5 mmol/l, HbA1c 6.6% (6.5; 7.7), 66.7% of the children had a history of glucosuria and 33.3% suffered obesity. The normal fasting blood glucose and HbA1c levels were found in 22.2% of the children. In 100% of the cases, results of OGTT suggested diabetes despite insulin secretion. Low titers of anti-GAD and anti-IA2 antibodies were detected in 20.0 and 22.2% of the children respectively. The most common mutation was p.P291fs.

scholarly journals Molecular genetic analysis of leucine tRNA in relevance to type 2 diabetes mellitus

2020 ◽  
Vol 9 (3) ◽  
pp. 167-173
Author(s):  
Niaz Muhammad Khan ◽  
Hayat Ullah ◽  
Abdur Raziq ◽  
Adnan Ali Khan ◽  
Muhammad Waseem Khan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Genetic Analysis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis

scholarly journals 25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: a clinical and molecular report on CYP2R1 mutations

2021 ◽  
Author(s):  
Sarah Bakhamis ◽  
Faiqa Imtiaz ◽  
Khushnooda Ramzan ◽  
Edward De Vol ◽  
Osamah AlSagheir ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Research Centre ◽  
Heterozygous Mutation ◽  
Hydroxylase Deficiency ◽  
Treatment And Prevention ◽  
Genetic Features ◽  
High Doses

Vitamin-D deficiency remains a major cause of rickets worldwide. Nutritional factors are the major cause and less commonly inheritance causes. Recently, CYP2R1 has been reported as a major factor for 25-hydroxylation contributing to the inherited forms of vitamin D deficiency. We conducted a prospective cohort study at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia to review cases with 25-hydroxylase deficiency and to describe their clinical, biochemical, and molecular genetic features. We analyzed 27 patients from 9 different families who presented with low 25-OH vitamin-D and not responding to usual treatment. Genetic testing identified two mutations: c.367+1G>A (12/27 patients) and c.768dupT (15/27 patients), where 18 patients were homozygous for their identified mutation and 9 patients were heterozygous. Both groups had similar clinical manifestations ranging in severity, but none of the patients with heterozygous mutation had hypocalcemic manifestations. 13/18 of homozygous patients and all the heterozygous patients responded to high doses of vitamin-D treatment, but they regressed after decreasing the dose, requiring lifelong therapy. 5/18 of homozygous patients required calcitriol to improve their biochemical data, whereas none of the heterozygous patients and patients who carried the c.367+1G>A mutation required calcitriol treatment. To date, this is the largest cohort series analyzeing CYP2R1-related 25-hydroxylase deficiency worldwide, supporting its major role in 25-hydroxylation of vitamin-D. It is suggested that a higher percentage of CYP2R1 mutations might be found in the Saudi population. We believe that our study will help in the diagnosis, treatment, and prevention of similar cases in the future.

Unusual clinical manifestations of type 1 neurofibromatosis

2011 ◽  
Vol 152 (49) ◽  
pp. 1965-1970
Author(s):  
Katalin Komlósi ◽  
Noémi Polgár ◽  
Kinga Hadzsiev ◽  
Gábor Ottóffy ◽  
Tamás Illés ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Final Diagnosis ◽  
Molecular Genetic Analysis ◽  
Café Au Lait Spots ◽  
Type 1 Neurofibromatosis ◽  
The Central Nervous System ◽  
Neurofibromin 1

Type 1 neurofibromatosis is an autosomal dominant hamartosis caused by mutations of the neurofibromin-1 gene. The classic features of the clinical phenotype include the presence of café-au-lait spots, neurofibromas, axillary and inguinal freckling, Lisch-nodules and deformities of the skeletal system, as well as the risk of developing multiple tumors, especially in the central nervous system. However, it is known from the literature that the phenotypic variability can pose a huge diagnostic difficulty. Aims: Our institute performs molecular genetic testing of the neurofibromin-1 gene since 2008; during this period several unusual phenotypic variants were found. Results, conclusion: The reported four cases represent interesting phenotypic variants or diagnostic challenges in which the final diagnosis was established by molecular genetic analysis. Orv. Hetil., 2011, 152, 1965–1970.

Molecular-genetic verification and treatment of neonatal diabetes mellitus related to the defects in ATP-dependent potassium channels: Results of the observation of 9 patients and the first description of ABCC8 gene mutations in Russia

2011 ◽  
Vol 57 (2) ◽  
pp. 3-8
Author(s):  
I I Dedov ◽  
Iu V Tikhonovich ◽  
Elena E Petriaikina ◽  
I G Rybkina ◽  
I É Volkov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Beta Cells ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Molecular Genetic Analysis ◽  
Neonatal Diabetes Mellitus ◽  
Molecular Genetic Study ◽  
Abcc8 Gene ◽  
Sound Therapy

Introduction of the methods for molecular-genetic analysis into clinical practice has opened up new prospects for both diagnosis and pathogenetically sound therapy of neonatal diabetes mellitus. It is currently known that the overwhelming majority of the cases of diabetes mellitus developing in children during the first six month of life are associated with defects of the genes controlling formation, development, and functional activity of pancreatic beta-cells whereas type 1 diabetes mellitus of autoimmune origin accounts for less than 1% of this pathology. This paper reports the results of a molecular-genetic study of 14 patients presenting with neonatal diabetes mellitus. Nine cases are shown to have developed as a result of mutations in KCNJ11 and ABCC8 genes. ABCC8 mutations are described for the first time in Russia. Analysis of clinical forms of neonatal diabetes mellitus revealed correlation between the type of mutations, clinical features of the disease, and susceptibility of the patients to sulfonylurea drugs.

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