scholarly journals A Novel Mutation inLeptinGene Is Associated with Severe Obesity in Chinese Individuals

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Yue Zhao ◽  
Nanchao Hong ◽  
Xiao Liu ◽  
Beibei Wu ◽  
Shanshan Tang ◽  
...  
Keyword(s):  
Severe Obesity ◽  
Novel Mutation ◽  
Single Gene ◽  
Clinical Syndrome ◽  
Nonsynonymous Mutation ◽  
Rare Type ◽  
Monogenic Obesity ◽  
Genetic And Environmental Factors ◽  
Clinical Measurements ◽  
Chinese Subjects

Obesity is a clinical syndrome which is driven by interactions between multiple genetic and environmental factors. Monogenic obesity is a rare type of obesity which is caused by a mutation in a single gene. Patients with monogenic obesity may develop early onset of obesity and severe metabolic abnormalities. In this study, we screened mutations ofLEPin a total of 135 Chinese individuals including 35 obese patients whose BMI ≥32 kg/m2and 100 controls with BMI <25 kg/m2. Moreover, detailed information and clinical measurements of the participants were also collected. Finally, we identified a novel nonsynonymous mutation H118L in exon 3 ofLEPin one patient with BMI 46.0 kg/m2. This mutation was not identified in the controls. We speculated that the mutation H118L inLEPmight be associated with severe obesity in Chinese subjects. However, the substantial mechanism should be further investigated.

Early-onset severe obesity due to complete deletion of the leptin gene in a boy

2017 ◽  
Vol 30 (11) ◽  
Author(s):  
Elif Ozsu ◽  
Serdar Ceylaner ◽  
Huseyin Onay
Keyword(s):  
Early Onset ◽  
Severe Obesity ◽  
Food Addiction ◽  
Single Gene ◽  
Gene Mutations ◽  
Metabolic Disturbances ◽  
Case Presentation ◽  
Monogenic Obesity ◽  
Abnormal Rate ◽  
Normal Body Weight

AbstractBackground:Monogenic obesity results from single gene mutations. Extreme obesity starting at an early age, especially in infancy, which is associated with endocrinopathy and metabolic disturbances is key to the diagnosis of monogenic obesity.Case presentation:A 6-month-old boy was admitted to our clinic with severe obesity and food craving. He was born with a birth weight of 3400 g to first-cousin parents. He started to gain weight at an abnormal rate at the age of 2 months. He had hyperinsulinemia, dyslipidemia and grade 2 hepatosteatosis. He had a 7-year-old, healthy brother with a normal body weight. Because of severe early-onset obesity and abnormal food addiction, his leptin level was measured and found to be 0.55 ng/mL (normal range for his age and sex is 0.7–21 ng/mL). AConclusions:To the best of our knowledge, a gross deletion of the

scholarly journals A Novel Homozygous Frameshift Mutation in Exon 2 of LEP Gene Associated with Severe Obesity: A Case Report

2016 ◽  
Vol 10 ◽  
pp. CMPed.S40432 ◽  
Author(s):  
Ashwaq Shukri Altawil ◽  
Horia Ahmad Mawlawi ◽  
Khalid Ateeq Alghamdi ◽  
Faten Fohaid Almijmaj
Keyword(s):  
Frameshift Mutation ◽  
Sequence Data ◽  
Direct Sequencing ◽  
Single Gene ◽  
Demographic Data ◽  
Normal Vaginal Delivery ◽  
Rare Type ◽  
Exon 2 ◽  
Monogenic Obesity ◽  
Lep Gene

Background Monogenic obesity is a rare type of obesity caused by a mutation in a single gene. Patients with monogenic obesity may develop early onset of obesity and severe metabolic abnormalities. Case Presentation A two-and-half-year-old girl was presented to our clinic because of excessive weight gain and hyperphagia. She was born at full term, by normal vaginal delivery with birth weight of 2.82 kg and no complications during pregnancy. The patient was the second child of two healthy, non-obese Saudis with known consanguinity. She gained weight rapidly leading to obesity at the age of three months. Methods The demographic data and clinical features were recorded. Blood samples were collected and tested for endocrine and metabolic characteristics and genetic studies. Mutations of the LEP gene were screened. The coding exons 2 and 3 and the corresponding exon–intron boundaries were amplified by polymerase chain reaction using specific primers, analyzed by direct sequencing using an ABI sequencer 3500 xL GA (Applied Biosystems), and evaluated using the JSI SeqPilot software. The resulting sequence data were compared with the reference MM_0002302. Conclusion We report a novel homozygous frameshift mutation c.144delin TAC (G1n49Thrfs*23) in exon 2 of the LEP gene associated with extreme obesity.

scholarly journals Krüppel-like factor 3 inhibition by mutated lncRNA Reg1cp results in human high bone mass syndrome

2019 ◽  
Vol 216 (8) ◽  
pp. 1944-1964 ◽  
Author(s):  
Mi Yang ◽  
Qi Guo ◽  
Hui Peng ◽  
Yu-Zhong Xiao ◽  
Ye Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Bone Mass ◽  
Noncoding Rna ◽  
Natural Compound ◽  
Novel Mutation ◽  
Gene Mutations ◽  
High Bone Mass ◽  
High Bone ◽  
Chinese Subjects

High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp. Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.

scholarly journals GENETICS IN ENDOCRINOLOGY: Genetic forms of severe insulin resistance: what endocrinologists should know

2013 ◽  
Vol 169 (4) ◽  
pp. R71-R80 ◽  
Author(s):  
Victoria E R Parker ◽  
Robert K Semple
Keyword(s):  
Insulin Resistance ◽  
Insulin Signalling ◽  
Polycystic Ovary ◽  
Single Gene ◽  
Clinical Syndrome ◽  
Glucose Lowering ◽  
Severe Insulin Resistance ◽  
Gene Defects ◽  
Lowering Activity

‘Insulin resistance’ (IR) is a widely used clinical term. It is usually defined as a state characterised by reduced glucose-lowering activity of insulin, but it is also sometimes used as a shorthand label for a clinical syndrome encompassing major pathologies such as type 2 diabetes, polycystic ovary syndrome, fatty liver disease and atherosclerosis. Nevertheless, the precise cellular origins of IR, the causal links among these phenomena and the mechanisms underlying them remain poorly understood or contentious. Prevalent IR usually results from a genetic predisposition interacting with acquired obesity; however, even in some lean individuals, very severe degrees of IR can be observed. It is important to identify these people as they often harbour identifiable single-gene defects and they may benefit from molecular diagnosis, genetic counselling and sometimes tailored therapies. Observation of people with known single-gene defects also offers the opportunity to make inferences about the mechanistic links between IR and common pathologies. Herein, we summarise the currently known monogenic forms of severe IR, with an emphasis on the practical aspects of their recognition, diagnosis and management. In particular, we draw distinctions among the biochemical subphenotypes of IR that arise from primary adipose tissue dysfunction or from primary insulin signalling defects and discuss the implications of this dichotomy for management.

scholarly journals “Touching Triton”:

2016 ◽  
Vol 78 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Madelene Loftin ◽  
Kelly East ◽  
Adam Hott ◽  
Neil Lamb
Keyword(s):  
Student Performance ◽  
Complex Disease ◽  
Disease Risk ◽  
Single Gene ◽  
Mendelian Inheritance ◽  
Serious Game ◽  
Genetic Technologies ◽  
Genetic And Environmental Factors ◽  
High Level ◽  
Unrealistic Expectations

Life science classrooms often emphasize the exception to the rule when it comes to teaching genetics, focusing heavily on rare single-gene and Mendelian traits. By contrast, the vast majority of human traits and diseases are caused by more complicated interactions between genetic and environmental factors. Research indicates that students have a deterministic view of genetics, generalize Mendelian inheritance patterns to all traits, and have unrealistic expectations of genetic technologies. The challenge lies in how to help students analyze complex disease risk with a lack of curriculum materials. Providing open access to both content resources and an engaging storyline can be achieved using a “serious game” model. “Touching Triton” was developed as a serious game in which students are asked to analyze data from a medical record, family history, and genomic report in order to develop an overall lifetime risk estimate of six common, complex diseases. Evaluation of student performance shows significant learning gains in key content areas along with a high level of engagement.

A novel mutation panel for predicting etoposide in small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20090-e20090
Author(s):  
Peng Luo ◽  
Zhengang Qiu ◽  
Anqi Lin ◽  
Kun Li ◽  
Weiyin Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Drug Sensitivity ◽  
Novel Mutation ◽  
Single Gene ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy

e20090 Background: Platinum-based chemotherapy, consisting of etoposide and cisplatin (EP), has been the cornerstone of therapy for extensive-stage small cell lung cancer (ES-SCLC) for decades. Despite the marked initial sensitivity of SCLC to chemotherapy, EP regimens cannot avoid the emergence of drug resistance in clinical practice. With the rise of new chemotherapy regimens in recent years and the primary resistance or insensitivity of ES-SCLC to EP regimens, it is desirable to be able to identify patients with resistant or insensitive ES-SCLC. Methods: The sequencing and drug sensitivity data of SCLC cell lines were provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC); the data regarding of sensitivity to etoposide of 54 SCLC cell lines were analyzed, and etoposide-sensitive cell lines and etoposide-resistant cell lines were differentiated according to the IC50 values defined by the GDSC. ROC curve analysis was performed on all mutations and combinations of mutations to select the optimal panel to predict resistance to etoposide. Results: Receiver Operating Characteristic(ROC) analysis of etoposide resistance revealed that the most significant single gene mutation indicating resistance to etoposide was CSMD3, and the accuracy of predicting resistance to etoposide proved to be the highest when there was any mutation in CSMD3/PCLO/RYR1/EPB41L3, area under the curve (AUC) = 0.804 (95% confidence interval (CI): 0.679-0.930, p < 0.001). Conclusions: This study found that a panel with four genes (CSMD3, EPB41L3, PCLO, and RYR1) can accurately predict sensitivity to etoposide. These findings provide new insights into the overall treatment for patients with ES-SCLC that is resistant or insensitive to etoposide.

scholarly journals Genetics of Adult Onset Stroke Subtypes: A Review of Current Knowldege and Future Prospects

2021 ◽  
Vol 7 (1) ◽  
pp. 79-86
Author(s):  
Muhammad Sougatul Islam ◽  
Bitali Islam ◽  
Munia Amin ◽  
ATM Hasibul Hasan
Keyword(s):  
Single Gene ◽  
Multisystem Disorder ◽  
Stroke Event ◽  
Vessel Occlusion ◽  
Stroke Subtypes ◽  
Risk Of Rupture ◽  
Genetic And Environmental Factors ◽  
9P21 Locus ◽  
Arachnoid Hemorrhage ◽  
Future Direction

The genetic contribution in stroke onset depends on the stroke subtypes. Understanding the genetic mechanism may influence the future direction in stroke management. There is complex interplay of genetic and environmental factors for any stroke event. Very small proportion of stroke is attributable to mendelian disorders. Stroke may also manifest as part of a syndromic disease in the form of single gene multisystem disorder. But there is no direct contribution of genetic polymorphism in conventional stroke subtypes. Specific genetic loci increase the suspectibility to development of hypertension, diabetes, dyslipideamia or influence the coagulation pathway or chance of atheroma formation and embolism. While chr9p21 locus or PITX2 and ZFHX3 are related to cardioemetabolic, HDAC9, TSPAN2 and 9p21 locus are responsible for the large vessel occlusion. On the otherhand, genome-wide significant locus on chromosome 1q22 the APOE locus are found to have significant association with intracerebral hemorrhage. But the direct pathophysiologic relationship of genetic plymorphirsm may be linked to onset of sub arachnoid hemorrhage. MMP-3, endothelial nitric oxide synthase (eNOS), tumor necrosis factor (TNF)-α, VCAM-1 etc have been found to be responsible for intracranial aneurysm formation, growth and risk of rupture. Journal of National Institute of Neurosciences Bangladesh, January 2021, Vol. 7, No. 1, pp. 75-86

scholarly journals Gene Therapy for Acute Respiratory Distress Syndrome

2022 ◽  
Vol 12 ◽  
Author(s):  
Jing Liu ◽  
David A. Dean
Keyword(s):  
Gene Therapy ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Single Gene ◽  
Treatment Strategies ◽  
The United States ◽  
Clinical Syndrome ◽  
Underlying Mechanisms

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.

scholarly journals Distinguishing differential susceptibility, diathesis-stress and vantage sensitivity: beyond the single gene and environment model

2017 ◽  
Author(s):  
Alexia Jolicoeur-Martineau ◽  
Ashley Wazana
Keyword(s):  
Effect Size ◽  
Single Gene ◽  
Differential Susceptibility ◽  
R Package ◽  
Small Samples ◽  
Environment Interaction ◽  
Environment Model ◽  
Genotype Environment Interaction ◽  
Multiple Genes ◽  
Genetic And Environmental Factors

Currently, two main approaches exist to distinguish differential susceptibility from diathesis-stress and vantage sensitivity in genotype × environment interaction (G×E) research: Regions of significance (RoS) and competitive-confirmatory approaches. Each is limited by their single-gene/single-environment foci given that most phenotypes are the product of multiple interacting genetic and environmental factors. We thus addressed these two concerns in a recently developed R package (LEGIT) for constructing G×E interaction models with latent genetic and environmental scores using alternating optimization. Herein we test, by means of computer simulation, diverse G×E models in the context of both single and multiple genes and environments. Results indicate that the RoS and competitive-confirmatory approaches were highly accurate when the sample size was large, whereas the latter performed better in small samples and for small effect sizes. The confirmatory approach generally had good accuracy (a) when effect size was moderate and N ≥ 500 and (b) when effect size was large and N ≥ 250, whereas RoS performed poorly. Computational tools to determine the type of G×E of multiple genes and environments are provided as extensions in our LEGIT R package.

Invited Review: Theories of aging

2003 ◽  
Vol 95 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Brian T. Weinert ◽  
Poala S. Timiras
Keyword(s):  
Gene Regulation ◽  
Life Span ◽  
Human Life ◽  
Single Gene ◽  
The Elderly ◽  
Body System ◽  
Functional Plasticity ◽  
Theories Of Aging ◽  
Genetic And Environmental Factors ◽  
Human Life Span

Several factors (the lengthening of the average and, to a lesser extent, of the maximum human life span; the increase in percentage of elderly in the population and in the proportion of the national expenditure utilized by the elderly) have stimulated and continue to expand the study of aging. Recently, the view of aging as an extremely complex multifactorial process has replaced the earlier search for a distinct cause such as a single gene or the decline of a key body system. This minireview keeps in mind the multiplicity of mechanisms regulating aging; examines them at the molecular, cellular, and systemic levels; and explores the possibility of interactions at these three levels. The heterogeneity of the aging phenotype among individuals of the same species and differences in longevity among species underline the contribution of both genetic and environmental factors in shaping the life span. Thus, the presence of several trajectories of the life span, from incidence of disease and disability to absence of pathology and persistence of function, suggest that it is possible to experimentally (e.g., by calorie restriction) prolong functional plasticity and life span. In this minireview, several theories are identified only briefly; a few (evolutionary, gene regulation, cellular senescence, free radical, and neuro-endocrineimmuno theories) are discussed in more detail, at molecular, cellular, and systemic levels.

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