dsg2 gene mutation

Pathogenic mutations in the DSG2 protein and structure of KCNE5 mutations. Studies investigating two heterozygous DSC2 mutations have shown that certain mutations in the N-terminal region can modify the subcellular localization of desmocollin-2 from the desmosomal plaque to the cytoplasm. DSG2 is expressed in many tissues, including the myocardium. 2,3 The majority of these mutations are insertion/deletion or nonsense mutations, which are expected to cause premature termination of the encoded proteins. DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy. Further supporting evidence for a pathogenic role comes from a report of a similar mutation at amino acid position 812 of DSG2 (heterozygous glycine to cysteine change: DSG2 G812C), which has been found to be causative for ARVC in a U.S. patient. KEGG is a database resource for understanding high-level functions and utilities of the biological system, such as the cell, the organism and the ecosystem, from molecular-level information, especially large-scale molecular datasets generated by genome sequencing and … Our findings here offer a novel pathway of CSTA regulation involving Dsg2 and a potential crosstalk between Dsg2 and CSTA that modulates cell adhesion. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in 8 probands (10%). Keratoderma with woolly hair. Gene symbol: Chromosomal location: Gene name: Mutation total: Log in: DSG2: 18q12.1: Desmoglein 2: 99 PMID: 16505173; mutations in DSG2 contribute to the development ofarrhythmogenic right ventricular dysplasia/cardiomyopathy PMID: 16773573 Conclusions Five novel heterozygous mutations (R158K, Q211X, L419S, A793D and N852fsX930) of PKP2 and three heterozygous mutations (R46G, D494A and F531C) of DSG2 were identified. An endomyocardial biopsy was obtained in 5, showing extensive … The disease is caused by mutations affecting the gene represented in this entry. However, the molecular pathomechanism of many DSG2 mutations is … DSG2 A gene on chromosome 18q12.1 that encodes desmoglein 2, a calcium-binding transmembrane glycoprotein component of desmosomes expressed in the colon, in colorectal carcinoma, and in other simple and stratified epithelial-derived cell lines. Interactions. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a disorder characterized by fibrofatty replacement of cardiac myocytes that typically manifests in the right ventricle. (2) Cardiac outcome could be stratified by mutation status and age. Awad MM, Dalal D, Cho E, Amat-Alarcon N, James C, Tichnell C, Tucker A, … Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10. Conclusions-Mutations in DSG2 and DSC2 are together less prevalent (10%) than PKP2 mutations (40%) in Dutch TFC+ ARVD/C patients. Interestingly, biallelic or digenic DSC2 and/or DSG2 mutations are frequently identified in TFC+ ARVD/C patients, suggesting that a single mutation is less likely to cause a full-blo … The study has revealed a greater frequency of occurrence of PKP2 mutations when compared to DSG2 mutations. DSG2 is an essential component of the desmosome so mutations of this gene disrupt the proper organization of desmosomal junctions. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. 7, 8 This process has been shown in classical cadherins to unmask the N-terminal EC1 domain and its tryptophan residue at position 2 (Trp-2), elements essential for Ca 2+-dependent trans-interactions. Both novel missense mutations DSG2 G812S and DSG2 C813R were absent in 400 control individuals. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in subjects with ARVC. 17 Because of the association between mutations in three components of the cardiac desmosome and ARVD/C, we analyzed probands with this disorder for mutations in DSG2, which encodes desmoglein-2. (provided by RefSeq, Jul 2008) GeneCards Summary for DSG2 Gene: DSG2 (desmoglein 2) is a protein-coding gene. The role of rare variants in DSG2 as causative mutations in Dilated Cardiomyopathy is described below. Abstract. Conclusions: The mutation of DSG2-F531C is a pathogenic mutation of ARVC, and further, DSG2-F531C caused ARVC in human and knock-in mice is gene dose-dependent. (3) Phenotypic influence on lethal VAs was less potent in truncating mutation carriers whose arrhythmic risk was independent of phenotype severity. Aims Mutations in the desmoglein-2 (DSG2) gene have been reported in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) but clinical information regarding the associated phenotype is at present limited. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in 8 probands (10%). Desmoglein-2 and Desmocollin-2 Mutations in Dutch Arrhythmogenic Right Ventricular Dysplasia/Cardiomypathy Patients: Results From a Multicenter Study The primary role of the desmosome is to adhere cells to each other, thus maintaining the structural integrity of skin and muscle tissues. This protein is part of the desmosome complex, which is present in both muscle and skin cells. Desmoglein-2 (DSG2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. The majority of causative variants are missense mutations, however, nonsense, small insertions or deletions, and splicing mutations have also been reported. All probands fulfilled task force criteria for ARVC. At least one mutation in the DSC2 gene has been found to cause a form of keratoderma with woolly hair classified as type III. In this study, we aimed to clinically characterize probands and family members carrying a DSG2 mutation. The DSG2 gene encodes the protein desmoglein-2. a secondary structure of DSG2 protein (NP_001934.2), which consists of 1118 amino acids. Mutations in DSG2 and DSP each account for approximately 10% to 15% of cases. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in 8 probands (10%). One of these probands has compound-heterozygous mutations in DSG2, and the remaining three have isolated heterozygous missense mutations, each disrupting known functional components of desmoglein-2. These results further support the recent human genetic findings that loss of function mutations in the CSTA gene result in skin fragility due to impaired cell-cell adhesion: autosomal-recessive exfoliative ichthyosis or acral peeling skin syndrome. There are some difference between patients with PKP2 mutation and that with DSG2 mutation … Interestingly, biallelic or digenic DSC2 and/or DSG2 mutations are frequently identified in TFC+ ARVD/C patients, suggesting that a single mutation is less likely to cause a full-blown ARVD/C phenotype. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Expression of Acta1 mRNA is increased in Dsg2 mutant myocardium. Desmocollin-2 has been shown to interact with: DSG2; JUP; References No association between mutations in this gene and human disease has been reported elsewhere. DSG1 (Desmoglein 1) is a Protein Coding gene. DSG2 mutations were predominant over those of PKP2 or other desmosomal genes. And immunofluorescence staining demonstrated the expression of CX43 decreased in intercalated discs. All probands fulfilled task force criteria for ARVC. Mutations in DSG2 and DSC2 are together less prevalent (10%) than PKP2 mutations (40%) in Dutch TFC+ ARVD/C patients. 28 Jan 2019, Gel status: 1 Created, Added New Source, Set mode of inheritance, Set Phenotypes Rebecca Foulger (Genomics England curator) gene: DSG2 was added gene: DSG2 … Mutations in the DSG2 gene are associated with rare but severe heart muscle diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC). All probands fulfilled task force criteria for ARVC. Haploinsufficiency phenotype comments: Desmoglein-2 (DSG2) is a member of the desmoglein family and is expressed in myocardium. It is inherited as an autosomal dominant disease with reduced penetrance, although autosomal recessive forms of the disease also occur. Therefore, ARVD is currently considered, at least in a subset, a disease of the cardiac desmosome. Because of this asymmetrical distribution of mutated genes, the effectiveness of this risk score to predict events in patients with DSP or DSG2 mutation was not guaranteed. Diseases associated with DSG1 include Erythroderma, Congenital, With Palmoplantar Keratoderma, Hypotrichosis, And Hyper-Ige and Palmoplantar Keratoderma I, Striate, Focal, Or Diffuse.Among its related pathways are Keratinization and Apoptotic execution phase. Diseases associated with DSG2 include arrhythmogenic right ventricular dysplasia 10, and cardiomyopathy, dilated, 1bb. Furthermore, in Cadrin‐Tourigny's study, among the 340 patients with mutations, 258 (76%) patients had a PKP2 mutation, while DSP was involved in 7% and DSG2 in 5% of patients. Am J Hum Genet 79:136-142, 2006). To identify early changes in gene expression that are caused by Dsg2 mutation, transcriptome profiles of heart tissue were determined for 2-week-old, macroscopically normal-appearing hearts of Dsg2 mt/mt mice and compared to those of matched hearts obtained from Dsg2 wt/wt and Dsg2 mt/wt mice (n=3 in each instance). These mutations, that account for ∼40% of DSG2 mutations, 2 are predicted to abolish DSG2 propeptide cleavage. An endomyocardial biopsy was obtained in 5, showing extensive … View mouse Dsg2 Chr18:20558074-20604521 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression These results show that DSG2-F531C mutation can destroy the structure of desmosome. 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