Identification of the pathogenic effects of missense variants causing PRKAG2 cardiomyopathy

Kömürcü-Bayrak, Evrim; Kalkan, Muhammed Abdulvahid; Çoban, Neslihan; Ozsait-Selcuk, Bilge; Bayrak, Fatih

doi:10.1016/j.abb.2022.109340

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…The involvement of PRKAB2 along with PRKAA2 has gained signi cance in lipid and glucose metabolism [58]. PRKAG2 has been widely associated with cardiomyopathy [59]. PRKAG1, on the other hand, is distributed throughout the organs and its association with obesity is yet to be concluded.…”

Section: Discussionmentioning

confidence: 99%

Predictive Analysis of the Leptin-Melanocortin and Adiponectin Signaling Pathways in Obesity through In Silico Techniques

Ghosh,

Dhar,

Roy

et al. 2024

Preprint

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Genetic and epigenetic alterations have been reported to significantly influence the global burden of obesity. Single nucleotide polymorphisms (SNPs) including both coding and non-coding amino acid changes are the key regulators of the protein structural and functional modifications. The current computational study utilizing in silico techniques focused on the screening and identification of the most pathogenic missense SNPs of the selected candidate genes of the leptin-melanocortin and adiponectin signaling pathways provoking obesity. A total of 2424 SNPs from 9 candidate genes were extracted from the NCBI database followed by pathogenicity prediction using seven servers, SIFT, PANTHER, Meta-SNP, PhD-SNP, PredictSNP, PolyPhen-2, and SNAP2. The shortlisted variants (n = 7) were analyzed for structural stability using DynaMut, iMutant, INPS3D, MuPro, and iStable followed by the functional stability analysis (n = 3) using Mut-Pred2, Project HOPE, and I-TASSER. Gene-network analysis of the finally screened SNPs (n = 3) was created using the STRING database. Two SNPs of ADIPOR1 (rs1419320091 and rs1654109863) and one variant of MC4R (rs1159323398) were predicted in the study to be the most pathogenic resulting in altered protein functionality. Therapeutic approaches designed based on early pathogenicity predictions using in silico analysis techniques would be a new horizon for the effective control of disease prevalence.

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Section: Discussionmentioning

confidence: 99%

Predictive Analysis of the Leptin-Melanocortin and Adiponectin Signaling Pathways in Obesity through In Silico Techniques

Ghosh,

Dhar,

Roy

et al. 2024

Preprint

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“…Another glycogen storage cardiomyopathy results from PRKAG2 (the gene encoding gamma-2 non-catalytic subunit of adenosine monophosphate-activated protein kinase) mutations on chromosome 7q36.1. The disease is characterized by left ventricular hypertrophy due to altered glycogen metabolism and glycogen storage in cardiac muscle, similar to Danon disease[ 301 - 303 ]. It is inherited in an autosomal dominant pattern.…”

Section: Gsds Involving Musclementioning

confidence: 99%

“…PRKAG2 gene variants cause a syndrome characterized by cardiomyopathy, conduction disease, and ventricular pre-excitation[ 302 ]. It may cause atrial fibrillation/flutter or conduction abnormalities that may cause sudden cardiac death and severe heart failure typically in the third and fourth decade[ 301 , 302 ]. Mutations in the gamma-2 non-catalytic subunit of AMP-activated protein kinase may cause lethal congenital storage disease of the heart, and death in the first year of life[ 303 ].…”

Section: Gsds Involving Musclementioning

confidence: 99%

Glycogen storage diseases: An update

Gümüş¹,

Özen²

2023

World J Gastroenterol

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Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.

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Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics

Wang¹,

Gao²,

Zhang³

et al. 2023

Biomedicine & Pharmacotherapy

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Identification of the pathogenic effects of missense variants causing PRKAG2 cardiomyopathy

Cited by 4 publications

References 46 publications

Predictive Analysis of the Leptin-Melanocortin and Adiponectin Signaling Pathways in Obesity through In Silico Techniques

Predictive Analysis of the Leptin-Melanocortin and Adiponectin Signaling Pathways in Obesity through In Silico Techniques

Glycogen storage diseases: An update

Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics

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