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 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.

scholarly journals Congenital Leptin Deficiency and Leptin Gene Missense Mutation Found in Two Colombian Sisters with Severe Obesity

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 342 ◽  
Author(s):  
Hernan Yupanqui-Lozno ◽  
Raul A. Bastarrachea ◽  
Maria E. Yupanqui-Velazco ◽  
Monica Alvarez-Jaramillo ◽  
Esteban Medina-Méndez ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Severe Obesity ◽  
Direct Sequencing ◽  
Genetic Disorder ◽  
Protein Product ◽  
Coding Region ◽  
Rare Type ◽  
Serum Leptin ◽  
Leptin Deficiency ◽  
Lep Gene

Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. Methods: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. Results: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G>T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. Conclusions: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America.

scholarly journals IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Renato Morato ZANATTO ◽  
Gianni SANTOS ◽  
Júnea Caris OLIVEIRA ◽  
Eduardo Marcucci PRACUCHO ◽  
Adauto José Ferreira NUNES ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Direct Sequencing ◽  
Colorectal Carcinogenesis ◽  
Kras Mutations ◽  
Primary Tumor Site ◽  
Exon 2 ◽  
Metastatic Site ◽  
Colorectal Cancer Patients

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

scholarly journals A Comparative Study to Assess the Level of Anxiety among Primi Gravida Mothers Planned for Normal Vaginal Delivery and Caesarean Section in the Selected Hospital, Agartala, West Tripura

2021 ◽  
Vol 6 (2) ◽  
pp. 58-61
Author(s):  
Ishita Nath
Keyword(s):  
Caesarean Section ◽  
Comparative Study ◽  
Vaginal Delivery ◽  
Demographic Variable ◽  
Demographic Data ◽  
Sampling Technique ◽  
Normal Vaginal Delivery ◽  
Research Approach ◽  
Perinatal Anxiety ◽  
Anxiety Screening

A comparative study was conducted among 100 primi gravida mothers (50 mothers in each group) from MCH clinic and IPD of IGM hospital, Agartala, West Tripura, who had planned for normal vaginal delivery and caesarean section. Research approach used was non experimental quantitative approach and research design was descriptive comparative design. Purposive sampling technique was used to draw the sample. Socio demographic data and modified Perinatal Anxiety Screening Scale were used to collect data from the samples through interview method. Analysis revealed that 52% of the primi gravida who had planned for caesarean section and 44% mothers who had planned for normal vaginal delivery had mild symptoms of anxiety. Mean anxiety score of the mothers who planned for caesarean section and normal vaginal delivery was 27.3 and 19.7 respectively, median 28.855 and 18.915 respectively and SD 7.0715 and 8.038 respectively. The mean difference was 7.6 and unpaired ‘t’ value was 5.0198, which was significant at p<0.05. Analysis of variance result showed that there was significant association between the level of anxiety of the primi gravida mothers who had planned for caesarean section with their selected socio demographic variable ‘occupation of husband’. The calculated ‘F’ value was 3.33 at p<0.05. The researcher concluded that the primi gravida mothers who had planned for caesarean section had more anxiety than the mothers who had planned for normal vaginal delivery and the anxiety level of the mothers who had planned for caesarean section was dependent on selected demographic variable occupation of the husband. Keywords:Anxiety, primi gravida, normal vaginal delivery, caesarean section.

scholarly journals Cascabel: A Scalable and Versatile Amplicon Sequence Data Analysis Pipeline Delivering Reproducible and Documented Results

2020 ◽  
Vol 11 ◽  
Author(s):  
Alejandro Abdala Asbun ◽  
Marc A. Besseling ◽  
Sergio Balzano ◽  
Judith D. L. van Bleijswijk ◽  
Harry J. Witte ◽  
...  
Keyword(s):  
Data Analysis ◽  
Sequence Data ◽  
Single Gene ◽  
Marker Gene ◽  
Gene Sequencing ◽  
Data Generation ◽  
Clustering Methods ◽  
Analysis Pipeline ◽  
Data Analysis Pipeline ◽  
Marker Gene Sequencing

Marker gene sequencing of the rRNA operon (16S, 18S, ITS) or cytochrome c oxidase I (CO1) is a popular means to assess microbial communities of the environment, microbiomes associated with plants and animals, as well as communities of multicellular organisms via environmental DNA sequencing. Since this technique is based on sequencing a single gene, or even only parts of a single gene rather than the entire genome, the number of reads needed per sample to assess the microbial community structure is lower than that required for metagenome sequencing. This makes marker gene sequencing affordable to nearly any laboratory. Despite the relative ease and cost-efficiency of data generation, analyzing the resulting sequence data requires computational skills that may go beyond the standard repertoire of a current molecular biologist/ecologist. We have developed Cascabel, a scalable, flexible, and easy-to-use amplicon sequence data analysis pipeline, which uses Snakemake and a combination of existing and newly developed solutions for its computational steps. Cascabel takes the raw data as input and delivers a table of operational taxonomic units (OTUs) or Amplicon Sequence Variants (ASVs) in BIOM and text format and representative sequences. Cascabel is a highly versatile software that allows users to customize several steps of the pipeline, such as selecting from a set of OTU clustering methods or performing ASV analysis. In addition, we designed Cascabel to run in any linux/unix computing environment from desktop computers to computing servers making use of parallel processing if possible. The analyses and results are fully reproducible and documented in an HTML and optional pdf report. Cascabel is freely available at Github: https://github.com/AlejandroAb/CASCABEL.

scholarly journals Mutation Spectrum and Genotype–Phenotype Analyses in a Pakistani Cohort With Hemophilia B

2017 ◽  
Vol 24 (5) ◽  
pp. 741-748 ◽  
Author(s):  
Muhammad Tariq Masood Khan ◽  
Arshi Naz ◽  
Jawad Ahmed ◽  
Tahir Shamsi ◽  
Shariq Ahmed ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Direct Sequencing ◽  
In Silico Analysis ◽  
Genetic Alterations ◽  
Factor Ix ◽  
Hemophilia B ◽  
Mutation Spectrum ◽  
Coagulation Activity ◽  
Exon 2 ◽  
Novel Variants

This study aimed to (1) identify F9 genetic alterations in patients with hemophilia B (HB) of Pakistani origin and (2) determine the genotype–phenotype relationships in these patients. Diagnosed cases of HB were identified through registries at designated tertiary health-care centers across the country. Consenting patients were enrolled into the study. The factor IX (FIX) coagulation activity (FIX:C) and key clinical features were recorded. Direct sequencing of F9 was carried out in all patients. All the variants identified were analyzed for functional consequences employing in silico analysis tools. Accession numbers from National Center of Biotechnology Information ClinVar database were retrieved for the novel variants. Genotype–FIX:C relationships were determined followed by FIX:C clinical phenotype assessment. A total of 52 patients with HB from 36 unrelated families were identified, which mainly comprised patients with moderate HB (n = 35; 67.3%). Among these, 35 patients from 22 unrelated families could be contacted and enrolled into the study. Missense variants were the most frequent (58.8%), followed by nonsense variants (17.6%). A missense, a short insertion, and a nonsense novel variants in exon 2, 6, and 7, respectively, were also identified. The disease manifested FIX:C heterogeneity in relation to the corresponding mutation in a significant number of cases. Clinical phenotype heterogeneity was also observed in relation to FIX:C-based severity assessment. We concluded that the registered FIX-deficient population of Pakistan mainly comprises moderate HB. F9 mutation spectrum in Pakistani patients with HB is heterogeneous. The HB population of Pakistan manifests a significant amount of genotype–FIX:C and FIX:C–clinical phenotype heterogeneities.

The molecular systematics of blowflies and screwworm flies (Diptera: Calliphoridae) using 28S rRNA, COX1 and EF-1α: insights into the evolution of dipteran parasitism

Parasitology ◽  
2011 ◽  
Vol 138 (13) ◽  
pp. 1760-1777 ◽  
Author(s):  
LAURA M. McDONAGH ◽  
JAMIE R. STEVENS
Keyword(s):  
Sequence Data ◽  
Single Gene ◽  
Nuclear Gene ◽  
Evolutionary Status ◽  
28S Rrna ◽  
Gene Trees ◽  
Data Set ◽  
Protein Coding ◽  
Nucleotide Sequence Data ◽  
The Family

SUMMARYThe Calliphoridae include some of the most economically significant myiasis-causing flies in the world – blowflies and screwworm flies – with many being notorious for their parasitism of livestock. However, despite more than 50 years of research, key taxonomic relationships within the family remain unresolved. This study utilizes nucleotide sequence data from the protein-coding genes COX1 (mitochondrial) and EF1α (nuclear), and the 28S rRNA (nuclear) gene, from 57 blowfly taxa to improve resolution of key evolutionary relationships within the family Calliphoridae. Bayesian phylogenetic inference was carried out for each single-gene data set, demonstrating significant topological difference between the three gene trees. Nevertheless, all gene trees supported a Calliphorinae-Luciliinae subfamily sister-lineage, with respect to Chrysomyinae. In addition, this study also elucidates the taxonomic and evolutionary status of several less well-studied groups, including the genus Bengalia (either within Calliphoridae or as a separate sister-family), genus Onesia (as a sister-genera to, or sub-genera within, Calliphora), genus Dyscritomyia and Lucilia bufonivora, a specialised parasite of frogs and toads. The occurrence of cross-species hybridisation within Calliphoridae is also further explored, focusing on the two economically significant species Lucilia cuprina and Lucilia sericata. In summary, this study represents the most comprehensive molecular phylogenetic analysis of family Calliphoridae undertaken to date.

scholarly journals Novel Point Mutations in the Dihydrofolate Reductase Gene of Plasmodium vivax: Evidence for Sequential Selection by Drug Pressure

2003 ◽  
Vol 47 (5) ◽  
pp. 1514-1521 ◽  
Author(s):  
Mallika Imwong ◽  
Sasithon Pukrittayakamee ◽  
Laurent Rénia ◽  
Franck Letourneur ◽  
Jean-Paul Charlieu ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Sequence Data ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Drug Pressure ◽  
Sequential Selection ◽  
Pcr Product ◽  
Reductase Gene ◽  
Antifolate Resistance ◽  
Type Sequence

ABSTRACT Mutations in the dihydrofolate reductase (dhfr) genes of Plasmodium falciparum and P. vivax are associated with resistance to the antifolate antimalarial drugs. P. vivax dhfr sequences were obtained from 55 P. vivax isolates (isolates Belem and Sal 1, which are established lines originating from Latin America, and isolates from patient samples from Thailand [n = 44], India [n = 5], Iran [n = 2], and Madagascar [n = 2]) by direct sequencing of both strands of the purified PCR product and were compared to the P. vivax dhfr sequence from a P. vivax parasite isolated in Pakistan (isolate ARI/Pakistan), considered to represent the wild-type sequence. In total, 144 P. vivax dhfr mutations were found at only 12 positions, of which 4 have not been described previously. An F→L mutation at residue 57 had been observed previously, but a novel codon (TTA) resulted in a mutation in seven of the nine mutated variant sequences. A new mutation at residue 117 resulted in S→T (S→N has been described previously). These two variants are the same as those observed in the P. falciparum dhfr gene at residue 108, where they are associated with different levels of antifolate resistance. Two novel mutations, I→L at residue 13 and T→M at residue 61, appear to be unique to P. vivax. The clinical, epidemiological, and sequence data suggest a sequential pathway for the acquisition of the P. vivax dhfr mutations. Mutations at residues 117 and 58 arise first when drug pressure is applied. Highly mutated genes carry the S→T rather than the S→N mutation at residue 117. Mutations at residues 57 and 61 then occur, followed by a fifth mutation at residue 13.

scholarly journals Becker muscular dystrophy caused by exon 2-truncating mutation of DMD

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Tetsuhiko Ikeda ◽  
Hidehiko Fujinaka ◽  
Kiyoe Goto ◽  
Takashi Nakajima ◽  
Tetsuo Ozawa
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Frameshift Mutation ◽  
Clinical Course ◽  
Becker Muscular Dystrophy ◽  
Exon 2 ◽  
Mild Phenotype ◽  
Frameshift Mutations ◽  
Stop Codons ◽  
Truncating Mutation

AbstractNonsense and frameshift mutations of the dystrophin (DMD) gene usually cause severe Duchenne muscular dystrophy (DMD). Interestingly, however, premature stop codons in exons 1 and 2 result in relatively mild Becker muscular dystrophy (BMD). Herein, we report the clinical course of a patient with a very mild phenotype of BMD caused by a frameshift mutation, NM_004006.2: c.40_41del GA/p.(Glu14ArgfsX17), in exon 2 of the DMD gene.

scholarly journals Leptin gene polymorphism of Ongole Grade cattle based on single nucleotide polymorphism

2018 ◽  
Vol 43 (4) ◽  
pp. 309
Author(s):  
N. Hilmia ◽  
D. Rahmat ◽  
D. Dudi
Keyword(s):  
Amino Acids ◽  
Single Nucleotide Polymorphism ◽  
Gene Polymorphism ◽  
Direct Sequencing ◽  
Snp Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Exon 2 ◽  
Specific Allele ◽  
Polymerase Chain

Point mutation on exon 2 of leptin gene, which changes amino acid encoding from Arginine to Cysteine, may alters the physiological function of the leptin hormone. This study aimed to identify leptin gene polymorphism of Ongole Grade (OG) cattle based on Single Nucleotide Polymorphism (SNP). The DNA sample was taken from 48 head of OG cattle at Balai Pengembangan Perbibitan Ternak Sapi Potong(BPPT SP) Cijeungjing West Java, which was isolated from white blood cell using the high salt method. Amplification of DNA was done by Polymerase Chain Reaction (PCR), followed by direct sequencing to obtain nucleotide sequence. The SNP analysis was carried out from alignment of sequencing result using Bioedit and MEGA 5.2 program. The results indicated in exon 2 leptin gene of OG cattle there was one synonymous SNPs that did not changeamino acids Serine encoding on g.1025T >C/S17S, while two non synonymous SNPaltered amino acids encoding, those were g.1047C> T /R25C and g.1048G>A/R25H. Those mutations changed amino acids encoding from Arginine to Cysteine and Arginine to Histidine respectively.In OG cattle, the frequency of A allele (44.8%) was higher than C allele (33.3%) and T allele (21.9%). Six genotypes were also identified, i.e. AA (41.7%), CC (20.8%), CT (20.8%), CA(4.2%), TT (10.4%) and TA (2.1 %). Heterozigosity of OG cattle based on leptin gene was 0.65 that was a high category. The A allele was a specific allele on Indonesian local cattle.

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