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 diagnosis of neurofibromatosis type I

2011 ◽  
Vol 152 (11) ◽  
pp. 415-419 ◽  
Author(s):  
Noémi Polgár ◽  
Katalin Komlósi ◽  
Kinga Hadzsiev ◽  
Tamás Illés ◽  
Béla Melegh
Keyword(s):  
De Novo ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Neurofibromatosis Type ◽  
Type I ◽  
De Novo Mutations ◽  
Presenting Symptoms ◽  
Type 1 Neurofibromatosis ◽  
Neurofibromin 1

Type 1 neurofibromatosis is an autosomal dominant hamartosis, caused by mutations of the gene neurofibromin-1. The variable clinical phenotype is characterized by café-au-lait spots, benign neurofibromas, axillary, inguinal hyperpigmentations, iris hamartomas, skeletal deformities and risk of neurofibroma-development. Pathogenic variations of neurofibromin-1 arise as de novo mutations in approx. 50% of the cases. Aims: Molecular genetic testing of neurofibromin-1 gene has been performed in our department since 2008; the following report summarizes our experiences. Methods: 40 patients, presenting symptoms of type 1 neurofibromatosis, were screened by sequencing or multiplex ligation-dependent probe amplification. Results: Pathogenic alterations were identified in 31 cases, 8 patients presented novel mutations. In 8 affected, no mutations were detected by sequencing; one of these patients had a deletion affecting the entire gene. Conclusions: Sequencing of the neurofibromin-1 gene and screening for rearrangements are useful in identifying pathogenic alterations in most of the cases. Orv. Hetil., 2011, 152, 415–419.

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.

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 The Case of Fulminant Myocarditis

Kardiologiia ◽  
2019 ◽  
Vol 59 (9) ◽  
pp. 91-96
Author(s):  
V. A. Titov ◽  
A. A. Shishkova ◽  
L. B. Mitrofanova ◽  
S. V. Ivanova ◽  
D. A. Zverev ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Screening Method ◽  
Final Diagnosis ◽  
Hemodynamic Instability ◽  
Molecular Genetic Analysis ◽  
Severe Form ◽  
Acute Stage ◽  
Fulminant Myocarditis ◽  
Circulatory Support ◽  
Immunohistochemical Studies

Fulminant myocarditis (FM) is a severe form of inflammatory myocardial injury rapidly developing as acute heart failure, cardiogenic shock, or life-threatening disturbances of cardiac rhythm. FM requires intensive treatment including drug therapy, mechanical circulatory support, and in some cases – heart transplantation. Echocardiography can be used as a screening method of diagnostics. Magnetic resonance imaging of the heart often cannot be performed because of hemodynamic instability of a patient, therefore endomyocardial biopsy with histological and immunohistochemical studies as well as molecular-genetic analysis of obtained samples is required for final diagnosis. Prognosis of the disease is determined by histological picture. In most cases, after cessation of acute stage of the inflammatory process, FM has a favorable long-term prognosis. In this article we present a clinical case of FM and review of current literature on diagnosis and treatment of this disease.

scholarly journals Molecular Genetic Analysis of the Idd4 Locus Implicates the IFN Response in Type 1 Diabetes Susceptibility in Nonobese Diabetic Mice

2006 ◽  
Vol 176 (5) ◽  
pp. 2976-2990 ◽  
Author(s):  
Evgueni A. Ivakine ◽  
Omid M. Gulban ◽  
Steven M. Mortin-Toth ◽  
Ellen Wankiewicz ◽  
Christopher Scott ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Analysis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Diabetic Mice ◽  
Diabetes Susceptibility ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

scholarly journals Legius Syndrome in a 13 Month Old Boy: A Case Report

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Learning Disabilities ◽  
Case Report ◽  
Developmental Delay ◽  
Neurofibromatosis Type 1 ◽  
Autosomal Dominant ◽  
Clinical Manifestations ◽  
Neurofibromatosis Type ◽  
Café Au Lait Spots ◽  
Legius Syndrome

Legius syndrome is autosomal dominant and caused by mutations in the SPRED1 gene. Clinical manifestations include multiple cafe-au-lait spots, axillary/ inguinal freckling and a degree of macrocephaly, without the non-pigmentary signs of neurofibromatosis type 1 (NF1). Learning disabilities, developmental delay and ADHD are also known.

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