scholarly journals Two novel variants in DYRK1B causative of AOMS3: expanding the clinical spectrum

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Elvia C. Mendoza-Caamal ◽  
Francisco Barajas-Olmos ◽  
Elaheh Mirzaeicheshmeh ◽  
Ian Ilizaliturri-Flores ◽  
Carlos A. Aguilar-Salinas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Protein Function ◽  
In Silico ◽  
Metabolic Diseases ◽  
In Silico Analysis ◽  
Diagnostic Strategies ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Silico Analysis

Abstract Background We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. Results After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed impairment of the DYRK1B protein function by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. Conclusions Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

scholarly journals Two Novel Variants in DYRK1B causative of AOMS3: Expanding the Clinical Spectrum

2020 ◽  
Author(s):  
Elvia Cristina Mendoza-Caamal ◽  
Francisco Barajas-Olmos ◽  
Elaheh Mirzaeicheshmeh ◽  
Ian Ilizaliturri-Flores ◽  
Carlos Aguilar-Salinas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
In Silico ◽  
Metabolic Diseases ◽  
Diagnostic Strategies ◽  
Medical Interventions ◽  
Pathogenic Variants ◽  
Severe Hypertriglyceridemia ◽  
Novel Variants ◽  
First Time

Abstract Background: We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. Results: After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed protein affectation induced by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. Conclusions: Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

In silico analysis for the identification of micro-RNAs as genetic factors regulating obesity and type 2 diabetes

2017 ◽  
Vol 12 (S 01) ◽  
pp. S1-S84
Author(s):  
P Gottmann ◽  
A Kamitz ◽  
N Hallahan ◽  
M Jähnert ◽  
A Schürmann
Keyword(s):  
Type 2 Diabetes ◽  
In Silico ◽  
Genetic Factors ◽  
In Silico Analysis ◽  
Micro Rnas ◽  
Silico Analysis

scholarly journals IN SILICO ANALYSIS OF ACTIVE CONSTITUENTS OF SILYMARIN AS ΑLPHA-GLUCOSIDASE ENZYME INHIBITORS IN TYPE 2 DIABETES MELLITUS

2019 ◽  
pp. 225-229 ◽  
Author(s):  
AHMAD ZONOUBI ◽  
PRASHANTHA CN ◽  
D VISAGA PERUMAL ◽  
ZAHRA MAFIBANIASADI
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
In Silico ◽  
Enzyme Inhibitors ◽  
In Silico Analysis ◽  
Active Constituents ◽  
Alpha Glucosidase ◽  
Silico Analysis

Objective: Type 2 diabetes mellitus (T2DM) is an acute metabolic disorder, in which the vogue is increasing persistently globally. The maltase-glucoamylase/alpha-glucosidase inhibitor is an oral antidiabetic drug collectively, which is utilizing for regulating carbohydrates that ordinarily transformed into simple sugars and absorbed by the intestine. Researchers need to constantly explore alternative therapeutic strategies for the clinical management of DM due to the increased adverse event caused by conservative antidiabetic agents. The present study proposes a substitute drug to examine the seven bioactive phytocomponents of Silybum marianum (milk thistle) that can regulate the hyperglycemia by downregulating alpha-glucosidase and its activity. Methods: Different integrated web-based in silico tools and techniques were used to model the enzyme (receptor) as well as to determine the druggability of different active constituents of silymarin and their pharmacokinetics were predicted. Further, the active site of the enzyme was predicted followed by molecular docking method. Results: The results show silychristin A and silydianin having less carcinogenicity and strong interaction to the target protein (alpha-glucosidase) compare to the reference drugs (acarbose and miglitol) and these two molecules can be used for the best drug molecules in T2DM. Conclusion: In the proposed study, the in silico analysis helps researchers to utilize these compounds for clinical applications. The conclusion also suggests that synthetically and semi-synthetically, nucleus and peripheral modifications, either in the form of skeletal rearrangements or partial degradations as well as functional group addition and replacement of the active molecules present in silymarin giving access to new structural motifs, which can be used in future as a lead compounds for antagonising the alpha-glucosidase in the treatment of diabetes mellitus.

scholarly journals GWAS identifies novel risk locus for erectile dysfunction and implicates hypothalamic neurobiology and diabetes in etiology

2018 ◽  
Author(s):  
Jonas Bovijn ◽  
Leigh Jackson ◽  
Jenny Censin ◽  
Chia-Yen Chen ◽  
Triin Laisk-Podar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Erectile Dysfunction ◽  
Genetic Risk ◽  
In Silico ◽  
Mendelian Randomization ◽  
In Silico Analysis ◽  
Risk Locus ◽  
Silico Analysis

AbstractGWAS of erectile dysfunction (ED) in 6,175 cases among 223,805 European men identified one new locus at 6q16.3 (lead variant rs57989773, OR 1.20 per C-allele; p = 5.71×10−14), located between MCHR2 and SIM1. In-silico analysis suggests SIM1 to confer ED risk through hypothalamic dysregulation; Mendelian randomization indicates genetic risk of type 2 diabetes causes ED. Our findings provide novel insights into the biological underpinnings of ED.

In Silico Analysis of New Potent Anti-hyperglycemic Molecule for Diabetes Type 2 Management

2019 ◽  
Vol 26 (2) ◽  
pp. 1031-1042
Author(s):  
Kritika Singh ◽  
Praveen Kumar Tripathi ◽  
Vinay Kumar Singh ◽  
Ashok Kumar Patel ◽  
O. N. Srivastava ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Diabetes Type 2 ◽  
Diabetes Type ◽  
Silico Analysis

scholarly journals Genetics A Comprehensive In Silico Analysis of Deleterious SNPs of Paraplegin Protein Associated with Hereditary Spastic Paraplegia through Mitochondrial Dysfunction

2020 ◽  
Vol 2 (2) ◽  
pp. 1-14
Author(s):  
Ammara Akhtar ◽  
Sobia Nazir Choudhry ◽  
Rana Muhammad Mateen ◽  
Mureed Hussain
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
In Silico ◽  
Mitochondrial Protein ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
Spastic Paraplegia ◽  
Bioinformatic Tools ◽  
Pathogenic Variants ◽  
Structural And Functional Properties ◽  
Silico Analysis

Hereditary spastic paraplegia (HSP) is a heterogenous neurological disorder primarily associated with progressive spasticity. Paraplegin is a mitochondrial protein and mutations in this protein can lead to HSP. In this study, in silico analysis was carried out to identify the pathogenic variants of SPG7 (paraplegin protein). To find novel pathogenic mutations, missense and splicing variants were collected from gnomAD database and passed through a detailed and stringent analysis with the help of a variety of bioinformatic tools. The list of mutations was examined and compared in ClinVar. Altogether, 14 missense mutations and 18 splicing mutations were obtained and these mutations were predicted to have the potential of disrupting the normal structural and functional properties of paraplegin protein.

scholarly journals A Novel Missense Variant in the ESRRB Gene Causing Nonsyndromic Hearing Loss: In Silico Analyses of a Case

2021 ◽  
Author(s):  
Tohid Ghasemnejad ◽  
Mahmoud Shekari Khaniani ◽  
Jafar Nouri Nojadeh ◽  
Sima Mansoori Derakhshan
Keyword(s):  
Hearing Loss ◽  
In Silico ◽  
Standard Procedure ◽  
In Silico Analysis ◽  
Missense Variant ◽  
12S Rrna ◽  
Pathogenic Variants ◽  
Genetic Hearing Loss ◽  
Syndromic Hearing Loss ◽  
Silico Analysis

Abstract Background: Genetic hearing loss (GHL) is a common heterogeneous disorder that can affect all ages, ethnicities, and genders. The most common form of hearing loss (HL) is autosomal recessive non-syndromic hearing loss (ARNSHL) and in most cases specific genotype-phenotype correlation is indistinguishable. This study aimed to identify the genetic cause of hearing loss in an Iranian Azeri Turkish ethnicity family with consanguine marriage which is negative for GJB2, GJB6 and mitochondrially encoded 12S RRNA (MT-RNR1) deleterious mutations.Methods: Targeted genome sequencing was applied for the detection of possible genetic causes of HL in this family. Co-segregation and in silico analysis of variant was performed by standard procedure.Results: A missense variant, c.499G>A, was identified in the ESRRB gene. Healthy and affected members of the family confirmed co-segregation of the variant with ARNSHL in the pedigree and then the pathogenicity of the variant was confirmed by in silico analysis and ACMG Guidelines. Conclusion: We report a novel missense variant in the ESRRB gene which seems to be a pathogenic variant. The result of this study suggests that the genetic background of hearing loss patients plays important role in the pathogenicity; moreover, targeted genomic capture is a powerful method that can discover pathogenic variants in heterogeneous disorders.

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