The Role of Cumulative Genetic Defects in NF1 Tumorigenesis

1999 ◽  
Author(s):  
Margaret Wallace
Keyword(s):  
Genetic Defects

scholarly journals P1805UNEXPECTD COMPLEMENT GENES ABNORALITIES IN CHILDREN WITH SECONDARY HEMOLITIC UREMIC SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Luigi Cirillo ◽  
Francesca Becherucci ◽  
Francesco Guzzi ◽  
Carmela Errichiello ◽  
Elisa Buti ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Background ◽  
Case Series ◽  
Cobalamin Deficiency ◽  
Genetic Defects ◽  
Next Generation ◽  
Atypical Hus ◽  
Uremic Syndrome ◽  
Generation Sequencing

Abstract Background and Aims Secondary hemolytic-uremic syndrome (HUS) is currently defined in the absence of genetic defects in complement genes (primary or atypical HUS, aHUS) or Shiga-toxin producing E. Coli infection (STEC-HUS). However, the role of complement genes abnormalities in secondary HUS is still a matter of debate as results coming from studies performed in adults are controversial. Moreover, genetic defects of complement regulation have been recently described in children with STEC-HUS, thus challenging the current HUS classification. The identification of a role of complement genes abnormalities in these patients could have important clinical implications for diagnosis and treatment. In this study, we assessed the presence of complement genes abnormalities in children with secondary HUS. Method We describe a case series of pediatric patients diagnosed with secondary HUS. All patients were screened for the presence of ADAMTS13 auto-antibody and ADAMTS13 deficiency. We performed next-generation sequencing for a panel of complement genes reported in association with aHUS (CFH, CFI, MCP, C3, FB, and THBD). Copy number variations and hybrid genes assessment were included in the analysis. Results Four patients aged 1-4 years with a diagnosis of sporadic secondary HUS were included in the study. HUS was secondary to glomerulopathy, cobalamin deficiency, bone marrow transplantation, and pneumococcal pneumoniae. Two out of four patients showed hypocomplementaemia (both C3 and C4). Diarrhea was a common clinical feature in all patients at onset, and none of these patients showed neurologic involvement. Renal replacement therapy was required in two patients at onset. Only one patient did not recover kidney function, and subsequently underwent kidney transplantation. Next-generation sequencing showed genetic abnormalities in all the patients (Table 1). All but one genetic variants have already been described in association with atypical HUS. Interestingly, haplotypes in CHF and MCP were present in three patients, all of Caucasian ethnicity. Conclusion According to the current HUS classification, complement abnormalities are diagnostic of aHUS. However, results coming from pediatric cohorts of STEC-HUS patients already claimed a role for genetic background also outside the aHUS spectrum, suggesting that the current terminology lacks both specificity and suggestion of cause. In this case series, complement genes abnormalities were present in all patients. Whether confirmed in larger cohorts, these findings would support the role of genetic background even in secondary HUS, suggesting the need for a revision of the current HUS classification, in agreement with the pathogenic mechanisms, in order to tailor the optimal treatment.

scholarly journals The enzyme succinate dehydrogenase (SDH) and its role in hereditary pituitary adenomas

2013 ◽  
Vol 10 (4) ◽  
pp. 10-15
Author(s):  
Iu V Pankratova ◽  
E G Przhiyalkovskaya ◽  
E A Pigarova ◽  
L K Dzeranova
Keyword(s):  
Pituitary Adenomas ◽  
Multiple Endocrine Neoplasia ◽  
Germline Mutations ◽  
Genetic Defects ◽  
Hereditary Syndromes ◽  
Pituitary Tumorigenesis ◽  
Active Research ◽  
Familial Pituitary Adenomas

Despite active research involving familial pituitary adenomas and characterization of five hereditary syndromes, the genetic defects in more than 80 - 95% of patients remain not found. Besides, there is more than 25 cases of coexistence of pheochromocytomas and pituitary adenomas described in literature that up to date is not integrated in any syndrome; genetic defects of such coexistence also aren't defined. However it is supposed that in pituitary tumorigenesis, germline mutations of SDH can take part that is obviously important aspect of further investigation. Germline mutations of SDH were found in patients with different phenotypes of pituitary adenomas. Studying of mutations in genes SDHD, SDHB, SDHC, SDHA and their prevalence in patients with familial pituitary adenomas or with phenotypes of multiple endocrine neoplasia without mutations in MEN1, CDKN1B, PRKAR1A, AIP genes can provide clarity in a role of mutations in SDH in endocrine and in particular pituitary tumorigenesis.

scholarly journals Genetic Diseases That Predispose to Early Liver Cirrhosis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Manuela Scorza ◽  
Ausilia Elce ◽  
Federica Zarrilli ◽  
Renato Liguori ◽  
Felice Amato ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Diseases ◽  
Laboratory Tests ◽  
Genetic Diseases ◽  
Genetic Defects ◽  
Pathogenic Role ◽  
Invasive Approach ◽  
Specific Diagnosis ◽  
Enzyme Transport

Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy.

scholarly journals Molecular genetic defects in congenital hypothyroidism

2004 ◽  
pp. U39-U44 ◽  
Author(s):  
A Gruters ◽  
H Krude ◽  
H Biebermann
Keyword(s):  
Central Nervous System ◽  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Critical Role ◽  
Genetic Defects ◽  
Cns Development ◽  
Central Hypothyroidism ◽  
Molecular Defects ◽  
The Central Nervous System

Recently molecular genetic defects in some cases of congenital hypothyroidism (CH) as well as of rare cases of central hypothyroidism have been identified. These studies have led to the description of so far unexplained forms of these disorders. In some patients with CH early diagnosis by newborn screening and early treatment was not able to lead to a normal mental development. This could subsequently be explained by molecular defects of transcription factors (FOXE-1/FKHL15, NKX2.1) which are important not only for the embryonic development of the thyroid gland but also for other organs including the central nervous system (CNS). These findings will help in understanding the critical role of thyroid hormones in the pre-and postnatal CNS development. However, many questions regarding the molecular defects and their consequences in the majority of patients with CH still remain open and will be addressed in this article.

scholarly journals Myocarditis: Which Role for Genetics?

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Chiara Baggio ◽  
Giulia Gagno ◽  
Aldostefano Porcari ◽  
Alessia Paldino ◽  
Jessica Artico ◽  
...  
Keyword(s):  
Genetic Background ◽  
Clinical Course ◽  
Risk Profile ◽  
Myocardial Inflammation ◽  
Genetic Defects ◽  
Prognostic Role ◽  
Clinical Presentations

Abstract Purpose of Review Myocarditis is a polymorphic disease, both in its presentation and clinical course. Recent data suggests that the genetic background, interacting with environmental factors, could be diriment both in the susceptibility and evolution of myocarditis in different clinical presentations. The aim of this paper is to expose the current available evidences and the evolving concepts on this topic, in order to provide insight for improving the clinical management of those patients. In this regard, the main goal is an optimal characterization of each patient’s risk, with the purpose of individualizing the treatment and the follow-up. Recent Findings The latest research highlights the possible prognostic role of some pathogenic mutations that could create a vulnerable myocardium prone to myocardial inflammation and also to the development of a long-lasting cardiomyopathy. Summary The identification of these genetic defects and of myocarditis patients requiring genetic testing is emerging as a challenge for the future. In fact, identifying a possible genetic background responsible for a particularly high-risk profile could be of extreme importance in improving management of myocarditis. This and many other aspects in the genetics of myocarditis remain uncovered, and further studies are expected based to refine our daily clinical practice.

scholarly journals The role of nutrigenetics in diet personalisation

2021 ◽  
Vol 11 (8) ◽  
pp. 75-79
Author(s):  
Karolina Rogulska ◽  
Aleksandra Strońska ◽  
Konrad Grzeszczak
Keyword(s):  
Association Studies ◽  
Control Group ◽  
Genetic Defects ◽  
Lactase Deficiency ◽  
Food Components ◽  
Disease Occurrence ◽  
Disease Entities ◽  
Further Development ◽  
Selection Of

Nutrigenetics is the field that studies genetic differences in relation to food components. It also examines the risk of food-dependent diseases. The search for genes responsible for disease occurrence is very difficult because the human genome has about 25,000 genes. Association studies are used to identify the relevant genes, and then the presence of polymorphisms is compared with a group of healthy people (control group). Thanks to these tests, it is possible to take an individual approach to the patient and arrange a personalized diet, which results in obtaining the best results. This article focuses on selected diseases including lactase deficiency, celiac disease, phenylketonuria and folate deficiency. In each of these diseases thanks to molecular research, it is possible to detect genetic defects, and then to apply a personalized diet which excludes or provides certain food products. Further development of nutrigenetics in the future will allow even better selection of diets in other disease entities.

scholarly journals Genetic defects and the role of helper T-cells in the pathogenesis of common variable immunodeficiency

2014 ◽  
Vol 3 (1) ◽  
pp. 2 ◽  
Author(s):  
Roya Sherkat ◽  
Vida Homayouni ◽  
Rahim Farahani ◽  
Reza Yazdani ◽  
MazdakGanjalikhani Hakemi
Keyword(s):  
T Cells ◽  
Common Variable Immunodeficiency ◽  
Helper T Cells ◽  
Genetic Defects ◽  
Common Variable

Clinical Insights Derived From B-Cell Immunodeficiency Disorders

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-19-SCI-19
Author(s):  
David Rawlings
Keyword(s):  
B Cell ◽  
Immune Function ◽  
Conflicts Of Interest ◽  
B Cell Development ◽  
Genetic Defects ◽  
Immune Disorders ◽  
Immune Development ◽  
New Information ◽  
Human Immune

Abstract Abstract SCI-19 Over the last four decades, the genetic defects leading to more than 140 distinct inherited immune disorders have been discovered. A subset of these diseases primarily impact B cell development, homeostasis, and/or activation. This talk will provide an overview of these B cell disorders. It will highlight new information regarding human immune function that has been gained from studying these disorders including: the role of key receptors or signaling effectors in immune development or activation, how such changes may impact pathogen specific versus autoimmune responses, and how targeting these pathways may provide a means to modulate other more common human immune diseases. Finally, we will provide a brief overview of efforts to correct one of these disorders in patients using genetic therapies. Disclosures: No relevant conflicts of interest to declare.

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