ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- PPA2 activates MTFP1-DNM1L fission signaling to govern mitochondrial proliferation and mitophagy.Autophagy · 2026Article
- Acute heart failure in adulthood as the first manifestation of a homozygous pyrophosphatase 2 variant, expanding the phenotypic spectrum: a case report.European heart journal. Case reports · 2025Article
- Nonischemic Cardiomyopathy in Adult-Onset PPA2-Deficient Mitochondrial Disease.JACC. Case reports · 2025Article
- PPA2 deficiency-a rare cause of genetic cardiomyopathy: a case report.European heart journal. Case reports · 2025Article
- A case of resuscitated cardiac arrest in a school-aged child with pyrophosphatase 2 deficiency.HeartRhythm case reports · 2025Article
- Conformational Dynamics of Mitochondrial Inorganic Pyrophosphatase hPPA2 and Its Changes Caused by Pathogenic Mutations.Life (Basel, Switzerland) · 2025Article
- PPA1 Deficiency Causes a Deranged Galactose Metabolism Recognizable in Neonatal Screening.Metabolites · 2023Article
- The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overview.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
- PPA2 Deficiency in 2 Sisters: A Rare Cause of Sudden Cardiac Death.JACC. Case reports · 2023Article
- OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases.Communications biology · 2023Article
- Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies.Nature cardiovascular research · 2023Article
- [Molecular medicine: pathobiochemistry as the key to personalized treatment of inherited diseases].Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
60 authors at 20 institutions in 9 countries.
Funding
Abstract
purposeBiallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants.
methodsSynthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized.
resultsAmong the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity.
conclusionWe expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.