ArticleEBioMedicine2020
Lifetime risk of autosomal recessive mitochondrial disorders calculated from genetic databases.
Article in EBioMedicine, 2020. 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 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- The burden of mitochondrial disease with associated seizures: systematic literature reviews of health-related quality of life, utilities, costs and healthcare resource use data.Orphanet journal of rare diseases · 2023Pooled it
- Mitochondrial Disease and Hearing Loss in Children: A Systematic Review.The Laryngoscope · 2022Pooled it
- Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.EMBO molecular medicine · 2026Article
- Estimating Lifetime Risk of Autosomal Recessive Kidney Diseases Using Population-Based Genotypic Data.Kidney international reports · 2025Article
- Identification of genetic mechanisms of non-isolated auditory neuropathy with various phenotypes in Chinese families.Orphanet journal of rare diseases · 2025Article
- Expanding the Epidemiological and Phenotypic Spectrum of MEGDEL Syndrome: The First Case Report From Egypt.Clinical medicine insights. Pediatrics · 2025Article
- Mitochondrial membrane synthesis, remodelling and cellular trafficking.Journal of inherited metabolic disease · 2025Review
- Review
- Epidemiology and natural history of POLG disease in Norway: a nationwide cohort study.Annals of clinical and translational neurology · 2024Article
- Primary mitochondrial disorders and mimics: Insights from a large French cohort.Annals of clinical and translational neurology · 2024Article
- Article
- Using genomic databases to determine the frequency and population-based heterogeneity of autosomal recessive conditions.Genetics in medicine open · 2024Article
- Distinct neonatal hyperammonemia and liver synthesis dysfunction: case report of a severe MEGDHEL syndrome.Frontiers in pediatrics · 2024Article
- Human model of primary carnitine deficiency cardiomyopathy reveals ferroptosis as a novel mechanism.Stem cell reports · 2023Article
- Drug Drop Test: How to Quickly Identify Potential Therapeutic Compounds for Mitochondrial Diseases Using YeastInternational journal of molecular sciences · 2023Review
- Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models.International journal of molecular sciences · 2023Review
- Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis.Orphanet journal of rare diseases · 2023Article
- A robust pipeline for ranking carrier frequencies of autosomal recessive and X-linked Mendelian disorders.NPJ genomic medicine · 2022Article
- Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Review
- Genetic Complementation of ATP Synthase Deficiency Due to Dysfunction of TMEM70 Assembly Factor in Rat.Biomedicines · 2022Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitochondrial disorders are a group of rare diseases, caused by nuclear or mitochondrial DNA mutations. Their marked clinical and genetic heterogeneity as well as referral and ascertainment biases render phenotype-based prevalence estimations difficult. Here we calculated the lifetime risk of all known autosomal recessive mitochondrial disorders on basis of genetic data.
methodsWe queried the publicly available Genome Aggregation Database (gnomAD) and our in-house exome database to assess the allele frequency of disease-causing variants in genes associated with autosomal recessive mitochondrial disorders. Based on this, we estimated the lifetime risk of 249 autosomal recessive mitochondrial disorders. Three of these disorders and phenylketonuria (PKU) served as a proof of concept since calculations could be aligned with known birth prevalence data from newborn screening reports.
findingsThe estimated lifetime risks are very close to newborn screening data (where available), supporting the validity of the approach. For example, calculated lifetime risk of PKU (16·0/100,000) correlates well with known birth prevalence data (18·7/100,000). The combined estimated lifetime risk of 249 investigated mitochondrial disorders is 31·8 (20·9-50·6)/100,000 in our in-house database, 48·4 (40·3-58·5)/100,000 in the European gnomAD dataset, and 31·1 (26·7-36·3)/100,000 in the global gnomAD dataset. The disorders with the highest lifetime risk (> 3 per 100,000) were, in all datasets, those caused by mutations in the SPG7, ACADM, POLG and SLC22A5 genes.
interpretationWe provide a population-genetic estimation on the lifetime risk of an entire class of monogenic disorders. Our findings reveal the substantial cumulative prevalence of autosomal recessive mitochondrial disorders, far above previous estimates. These data will be very important for assigning diagnostic a priori probabilities, and for resource allocation in therapy development, public health management and biomedical research.
fundingGerman Federal Ministry of Education and Research.
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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.