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| Dilated Cardiomyopathy v1.30 | PKP2 | Suliman Khan edited their review of gene: PKP2: Changed phenotypes: Cardiomyopathy, MONDO:0004994, PKP2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.30 | PKP2 | Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy, MONDO:0005021, PKP2-related; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.29 | PKP2 | Seb Lunke Publications for gene: PKP2 were set to 15489853; 16567567; 30562116; 35059364; 38050058 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.29 | PKP2 | Seb Lunke Publications for gene: PKP2 were set to 15489853; 16567567; 38050058 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.28 | PKP2 | Seb Lunke Mode of inheritance for gene: PKP2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.27 | PKP2 | Seb Lunke Classified gene: PKP2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.27 | PKP2 | Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.26 | PKP2 | Elena Savva Classified gene: PKP2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.26 | PKP2 | Elena Savva Gene: pkp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.25 | PKP2 | Elena Savva Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 (MIM#609040) to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.24 | PKP2 | Elena Savva Publications for gene: PKP2 were set to 15489853; 16567567 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.24 | PKP2 | Elena Savva Mode of inheritance for gene: PKP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v1.23 | PKP2 |
Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome. Sources: Literature; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome. |
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| Dilated Cardiomyopathy v1.23 | PKP2 | Suliman Khan reviewed gene: PKP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30562116, PMID: 35059364, PMID: 38050058; Phenotypes: Dilated cardiomyopathy, hypoplastic left heart syndrome, hydrops fetalis, ventricular septal defect, left ventricular non-compaction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.78 | PKP2 | Zornitza Stark Marked gene: PKP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.78 | PKP2 | Zornitza Stark Added comment: Comment when marking as ready: Included due to phenotypic overlap between ARVC and DCM, limited evidence for association with DCM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.78 | PKP2 | Zornitza Stark Gene: pkp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.78 | PKP2 | Zornitza Stark Classified gene: PKP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.78 | PKP2 | Zornitza Stark Gene: pkp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.76 | PKP2 | Paul De Fazio edited their review of gene: PKP2: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.76 | PKP2 |
Paul De Fazio gene: PKP2 was added gene: PKP2 was added to Dilated Cardiomyopathy. Sources: Literature Mode of inheritance for gene: PKP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PKP2 were set to 15489853; 16567567 Phenotypes for gene: PKP2 were set to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040) gene: PKP2 was marked as current diagnostic Added comment: Mutations in the PKP2 gene have been identified in individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC). This condition most commonly affects the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. ARVC increases the risk of an abnormal heartbeat (arrhythmia) and sudden death. https://ghr.nlm.nih.gov/gene/PKP2 PMID:15489853, 16567567 https://doi.org/10.1371/journal.pone.0100560 ClinVar reports 1 variants only in an individual with DCM annotated as “LP” p.(His679Thr). No data regarding the variant associated with DCM is reported in GnomAD, supporting its low prevalence. However, if this is a variant linked to a clinical phenotype that initially manifested as ACM and then evolved into DCM is yet to be assessed. Considering that clinically cardiomyopathies are diseases with a progressive course, one cannot exclude that DCM cases carrying Pkp2 variants could be cases of advanced Arrythmogenic Cardiomyopathy (ACM or ARVC) which were missed in the initial disease phases. (https://doi.org/10.3389/fcvm.2018.00184) Sources: Literature |
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