scholarly journals Genetic causes of severe childhood obesity: a remarkably high prevalence (≥49%) in an inbred population of Pakistan

2020 ◽  
Author(s):  
Ada Admin ◽  
Sadia Saeed ◽  
Muhammad Arslan ◽  
Jaida Manzoor ◽  
Sadia M. Din ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Point Mutations ◽  
Copy Number Variations ◽  
Coding Regions ◽  
New Genes ◽  
Whole Exome ◽  
High Prevalence ◽  
Severely Obese ◽  
Prevalence Of Obesity ◽  
Obese Subjects

Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance.

scholarly journals Genetic causes of severe childhood obesity: a remarkably high prevalence (≥49%) in an inbred population of Pakistan

2020 ◽  
Author(s):  
Ada Admin ◽  
Sadia Saeed ◽  
Muhammad Arslan ◽  
Jaida Manzoor ◽  
Sadia M. Din ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Point Mutations ◽  
Copy Number Variations ◽  
Coding Regions ◽  
New Genes ◽  
Whole Exome ◽  
High Prevalence ◽  
Severely Obese ◽  
Prevalence Of Obesity ◽  
Obese Subjects

Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance.

scholarly journals GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Antonello E. Rigamonti ◽  
Graziano Grugni ◽  
Marco Arreghini ◽  
Paolo Capodaglio ◽  
Alessandra De Col ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Tender Point ◽  
Fat Free Mass ◽  
Obese Women ◽  
Arginine Test ◽  
High Prevalence ◽  
Stimulation Tests ◽  
Severely Obese ◽  
Prevalence Of Obesity ◽  
Ghrh Plus Arginine Test

Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or <−2 SDS), underwent the combined GHRH plus arginine test. Four out of 16 obese women with FM (25%) had low IGF-1 SDS values, 2 cases of this subgroup (12.5%) failing also to normally respond to the test. Among patients with normal GH responses, 4 showed a delayed GH peak. The subgroup with low IGF-1 SDS values had higher BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

CNV Analysis in Monozygotic Twin Pairs Discordant for Urorectal Malformations

2013 ◽  
Vol 16 (4) ◽  
pp. 802-807 ◽  
Author(s):  
Friederike Baudisch ◽  
Markus Draaken ◽  
Enrika Bartels ◽  
Eberhard Schmiedeke ◽  
Soyhan Bagci ◽  
...  
Keyword(s):  
De Novo ◽  
Bladder Exstrophy ◽  
Anorectal Malformations ◽  
Monozygotic Twin ◽  
Regulatory Elements ◽  
Copy Number Variations ◽  
Molecular Karyotyping ◽  
Genetic Changes ◽  
Coding Regions ◽  
Whole Exome

Early post-twinning mutational events can account for discordant phenotypes in monozygotic (MZ) twin pairs. Such mutational events may comprise genomic alterations of different sizes, ranging from single nucleotides to large copy-number variations (CNVs). Anorectal malformations (ARM) and the bladder exstrophy-epispadias complex (BEEC) represent the most severe end of the urorectal malformation spectrum. Recently, CNV studies in patients with sporadic ARM and the BEEC have identified de novo events that occur in specific chromosomal regions. We hypothesized that early arising, post-twinning CNVs might contribute to discordance in MZ twin pairs with ARM or the BEEC; knowledge of such CNVs might help to identify additional chromosomal regions involved in the development of these malformations. We investigated four discordant MZ twin pairs (three ARM and one BEEC) using molecular karyotyping arrays comprising 1,140,419 markers with a median marker spacing of 1.5 kb. Filtering the coding regions for possible disease-causing post-twinning de novo CNVs present only in the affected twin, but not in the unaffected twin or the parents, identified a total of 136 CNVs. These 136 CNVs were then filtered against publicly available databases and finally re-evaluated visually. No potentially causative CNV remained after applying these filter criteria. Our results suggest that post-twinning CNV events that affect coding regions of the genome did not contribute to the discordant phenotypes in MZ twin pairs that we investigated. Possible causes for the discordant phenotypes include changes in regulatory elements or smaller genetic changes within coding regions which may be detectable by whole-exome sequencing.

Genetic landscape of sporadic vestibular schwannoma

2018 ◽  
Vol 128 (3) ◽  
pp. 911-922 ◽  
Author(s):  
Aril Løge Håvik ◽  
Ove Bruland ◽  
Erling Myrseth ◽  
Hrvoje Miletic ◽  
Mads Aarhus ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Pathway Analysis ◽  
Vestibular Schwannoma ◽  
Gamma Knife Radiosurgery ◽  
Copy Number Variations ◽  
Axonal Guidance ◽  
New Genes ◽  
Whole Exome ◽  
Genetic Landscape ◽  
Group A

OBJECTIVEVestibular schwannoma (VS) is a benign tumor with associated morbidities and reduced quality of life. Except for mutations in NF2, the genetic landscape of VS remains to be elucidated. Little is known about the effect of Gamma Knife radiosurgery (GKRS) on the VS genome. The aim of this study was to characterize mutations occurring in this tumor to identify new genes and signaling pathways important for the development of VS. In addition, the authors sought to evaluate whether GKRS resulted in an increase in the number of mutations.METHODSForty-six sporadic VSs, including 8 GKRS-treated tumors and corresponding blood samples, were subjected to whole-exome sequencing and tumor-specific DNA variants were called. Pathway analysis was performed using the Ingenuity Pathway Analysis software. In addition, multiplex ligation-dependent probe amplification was performed to characterize copy number variations in the NF2 gene, and microsatellite instability testing was done to investigate for DNA replication error.RESULTSWith the exception of a single sample with an aggressive phenotype that harbored a large number of mutations, most samples showed a relatively low number of mutations. A median of 14 tumor-specific mutations in each sample were identified. The GKRS-treated tumors harbored no more mutations than the rest of the group. A clustering of mutations in the cancer-related axonal guidance pathway was identified (25 patients), as well as mutations in the CDC27 (5 patients) and USP8 (3 patients) genes. Thirty-five tumors harbored mutations in NF2 and 16 tumors had 2 mutational hits. The samples without detectable NF2 mutations harbored mutations in genes that could be linked to NF2 or to NF2-related functions. None of the tumors showed microsatellite instability.CONCLUSIONSThe genetic landscape of VS seems to be quite heterogeneous; however, most samples had mutations in NF2 or in genes that could be linked to NF2. The results of this study do not link GKRS to an increased number of mutations.

Identification of Novel Genes Associated to Major Mental Disease by Whole Exome Sequencing in Families with High Prevalence

2017 ◽  
Vol 41 (S1) ◽  
pp. S98-S99
Author(s):  
J. Pol Fuster ◽  
L. Ruiz Guerra ◽  
B. Ortega Vila ◽  
A. Medina Dols ◽  
B. Bisbal Carrió ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Mental Disease ◽  
Psychotic Symptoms ◽  
Disease Etiology ◽  
New Genes ◽  
Whole Exome ◽  
High Prevalence ◽  
Rare Genetic Variants

IntroductionThe identification of new genetic variants underlying psychosis is crucial to improve its molecular diagnosis and to determine the disease etiology, which is necessary to develop new therapeutic targets.AimTo identify novel rare genetic variants associated to mental disorders, using whole exome sequencing (WES).MethodsTwo families with high prevalence of mental disease were genotyped using WES. The first family has 5 members affected, the mother with a bipolar disorder, three sons, two with schizophrenia and one with schizoaffective disorder, and a cousin with major depression and psychotic symptoms. The second family is constituted by 38 members affected by major mental diseases in three generations. Key affected members of each family were genotyped by WES. Shared rare variants, with allelic frequencies below 0.5% in general population, were identified among the affected members of the family. The segregation of those variants was confirmed by Sanger sequencing.ResultsIn family 1, thirty-seven genetic variants related to neurodevelopment were identified. Two of those variants in the genes TRIP12 and RNF25 segregated with psychosis. In family 2, seven rare genetic variants contained in genes related to neurodevelopment were identified. A mutation in the gene ARHGAP19 segregated with psychosis.ConclusionsThree new genes have been found to be associated with psychosis. TRIP12 and RNF25 encode two E3-ubiquitin ligases which modulate the Wnt pathway, mutations in which lead to neurodevelopmental defects. ARHGAP19 encodes a GTPase which regulates the RhoA protein, involved in the regulation of the cytoskeleton.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Polymorphism of the TMPRSS2 gene relating to COVID-19 subceptibility in Vietnamese population

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Nguyen Dang Ton ◽  
Vu Phuong Nhung ◽  
Duong Thu Trang ◽  
Nguyen Thi Thanh Hoa ◽  
Nguyen Hoai Nam ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Point Mutations ◽  
Vital Role ◽  
Host Cells ◽  
Sequencing Data ◽  
Coding Regions ◽  
Whole Exome ◽  
Whole Exome Sequencing Data ◽  
Vietnamese Population ◽  
Damage Protein

Recently, a contagious lung disease named coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly spread worldwide and has many serious consequences for human health. Human genetic polymorphisms may contribute to the variation of incidence, mortality as well as severity of COVID-19. To date, this factor in the Vietnamese population remains unknown. A cellular protease termed transmembrane protease serine 2 (TMPRSS2) was found to play a vital role in the entry of SARS-CoV-2 into host cells. In this study, we investigated polymorphisms in the TMPRSS2 gene from 270 whole exome sequencing data of Vietnamese peoples. We also employed bioinformatics tools including SIFT, Polyphen-2, and PROVEAN to predict the possible function of missense variants. A total of 34 TMPRSS2 variants were identified, of which, 29 were in non-coding regions and 14 were in coding regions. Variants found in exons included seven synonymous and seven non-synonymous point mutations, one of which was novel mutation (c.A1336C/p.R446R). Mutation c.G589A/p.V197M (rs12329760) possesses the highest frequency and was predicted to have the ability to damage protein by SIFT and Polyphen-2. In addition, the damaging possibility was also found in c.T244G/p.Y82D and c.C896T/p.A299V variants. This study contributes to the understanding of Vietnamese genetic variation databases relating to susceptibility to COVID-19. 

scholarly journals Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity

2021 ◽  
pp. 219256822110315
Author(s):  
Tsutomu Endo ◽  
Yoshinao Koike ◽  
Yuichiro Hisada ◽  
Ryo Fujita ◽  
Ryota Suzuki ◽  
...  
Keyword(s):  
Thoracic Spine ◽  
Ligamentum Flavum ◽  
Posterior Longitudinal Ligament ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cross Sectional ◽  
Risk Of Progression ◽  
Severely Obese ◽  
Prevalence Of Obesity ◽  
Obese Subjects

Study Design: Retrospective cross-sectional study. Objectives: There is insufficient data on the clinical features of ossification of the ligamentum flavum (OLF) of the thoracic spine and the risk of progression of ossified lesions. The link between obesity and ossification of the posterior longitudinal ligament (OPLL), which frequently coexists with OLF, has been demonstrated. However, the link between obesity and OLF has not been recognized. We aimed to determine the prevalence of obesity in thoracic OLF and whether the severity of OLF is associated with the degree of obesity. Methods: A total of 204 symptomatic Japanese subjects with thoracic OLF and 136 subjects without spinal ligament ossification as controls were included. OLF subjects were divided into 3 groups: 1) localized OLF (OLF <2-intervertebral regions); 2) multilevel OLF (OLF ≥3-intervertebral regions); and 3) OLF + OPLL. The severity of OLF was quantified using the OLF index using computed tomography imaging of the entire spine. Results: The proportion of severely obese subjects (BMI ≥ 30 kg/m2) was significantly higher both in the multilevel OLF group (25.5%) and the OLF + OPLL group (44.3%) than in the localized OLF group (3.6%) and the control group (1.4%) ( P < 0.01). BMI, age, and coexistence of cervical OPLL and lumbar OLF were associated with thoracic OLF index in the multiple regression analysis. Conclusions: Our findings demonstrated that obesity is a distinct feature of multilevel OLF in the thoracic spine and that the severity of OLF is associated with the degree of obesity.

scholarly journals Evaluation of Nutritional Risk and Prevalence of Obesity in Patients with Covid-19 in A Reference Hospital in Salvador, Bahia, Brazil: A Cross-Sectional Study

2021 ◽  
Vol 14 (01) ◽  
pp. 011-015
Author(s):  
Rodrigo Fernandes Weyll Pimentel ◽  
Gilson Cruz de Moraes ◽  
Shalla Gomes Cavalcanti Barcelos ◽  
Pedro Carlos Muniz de Figueiredo ◽  
Magno Conceição Das Merces
Keyword(s):  
Cross Sectional Study ◽  
Nutritional Risk ◽  
Sectional Study ◽  
Cross Sectional ◽  
High Prevalence ◽  
Reference Hospital ◽  
Prevalence Of Obesity ◽  
Nrs 2002 ◽  
Study Type ◽  
Nutritional Risk Screening

Abstract Introduction The Coronavirus has spread to almost every country in the world, causing the coronavirus disease (COVID-19). The coronavirus stands out among the other infections especially by it's high contagious power and important effects on the respiratory system. The COVID-19 has differents ways of presentation and these are influenced by the patient's previous nutricional status, correlated with the patient's lifestyle and comorbities. Objective this survey seeks to analyze the nutritional status and the prevalence of obesity in patients hospitalized with SARS-CoV-2. Methods: this is a descriptive, prospective and cross-sectional study type, which 41 patients affected by COVID-19 were interviewed. Patient's weight and height were used to assess the BMI, and nutritional risk assessment was performed using the Nutritional Risk Screening tool (NRS 2002). For the analysis, Absolute (AF) and Relative Frequency (RF), the mean and the standard deviation were calculated. Results It was observerd that 78% of the participants had a high nutritional risk, while only 22% had a low nutritional risk. Besides that, 34% showed overweight and 41.4% showed obesity. Conclusion the existence of a high prevalence of increased nutritional risk was evidenced, in addition to the high frequency of overweight in patients affected by SARS-CoV-2.

scholarly journals Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

2021 ◽  
Author(s):  
Wenhui Li ◽  
Wanjun Lei ◽  
Xiaopei Chao ◽  
Xiaochen Song ◽  
Yalan Bi ◽  
...  
Keyword(s):  
Copy Number ◽  
Somatic Mutations ◽  
Hpv Infection ◽  
Copy Number Variations ◽  
Cervical Adenocarcinoma ◽  
Structural Variations ◽  
Driver Genes ◽  
Genetic Changes ◽  
Genomic Changes ◽  
Whole Exome

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Sign in / Sign up

Export Citation Format

Share Document