Dilated and arrhythmogenic cardiomyopathy
Gene: PPA2
Comment on list classification: As reviewed by Matthew Edwards, there is sufficient evidence for this gene to be promoted to green rating at the next GMS review.Created: 8 Aug 2023, 5:46 p.m. | Last Modified: 8 Aug 2023, 5:46 p.m.
Panel Version: 2.14
PMID:34400813 reported 34 individuals from 20 unrelated families with rapidly progressive cardiac failure or sudden unexplained death in at least one family member and harboring biallelic PPA2 variants. Of these 34 individuals, only six remain alive and 23 died before the age of two. 12 individuals had dilated cardiomyopathy and nine had arrhythmia. The review of previous published reports showed there are four additional cases with dilated cardiomyopathy and eight additional cases with arrhythmia, bringing the total to 16 and 17 respectively.
This gene has been associated with relevant cardiac phenotypes in both OMIM (MIMs #617222 & #617223) and Gene2Phenotype (with 'definitive' rating in the DD panel).Created: 8 Aug 2023, 5:44 p.m. | Last Modified: 8 Aug 2023, 5:44 p.m.
Panel Version: 2.11
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Sudden cardiac failure, infantile, OMIM:617222; ?Sudden cardiac failure, alcohol-induced, OMIM:617223
Publications
Now a well established gene causing infantile sudden death, but can also manifest at a later age as alcohol-induced sudden death. Our lab and others have found several bi-allelic pathogenic variants in such SCD cases (see above ref). Is currently on syndromic/paediatric cardiomyopathy panel (R135) and mitochindrial panels, but wholly appropriate for this panel as well
Sources: Expert ReviewCreated: 9 Jun 2023, 3 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: ppa2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: PPA2 were changed from Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced to Sudden cardiac failure, infantile, OMIM:617222; ?Sudden cardiac failure, alcohol-induced, OMIM:617223
Publications for gene: PPA2 were set to PMID: 34400813
Tag Q3_23_promote_green tag was added to gene: PPA2. Tag Q3_23_NHS_review tag was added to gene: PPA2.
gene: PPA2 was added gene: PPA2 was added to Dilated and arrhythmogenic cardiomyopathy. Sources: Expert Review Mode of inheritance for gene: PPA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPA2 were set to PMID: 34400813 Phenotypes for gene: PPA2 were set to Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced Penetrance for gene: PPA2 were set to unknown Review for gene: PPA2 was set to GREEN gene: PPA2 was marked as current diagnostic