ArticleHuman genetics2008
The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level.
Article in Human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 117 citations in OpenAlex.
- Structure and Substrate Specificity of Human Short-Chain Acyl-CoA Dehydrogenase and Insights into Pathogenicity of Disease-Associated Mutations.International journal of molecular sciences · 2026Article
- Newborn screening, genetic analysis, and long-term follow-up of 89 cases with short-chain acyl-CoA dehydrogenase deficiency (SCADD).Molecular genetics and metabolism reports · 2026Article
- Article
- Structural insights into the pathogenicity of point mutations in human acyl-CoA dehydrogenase homotetramers.Journal of biological physics · 2024Article
- The Physiological and Pathological Role of Acyl-CoA Oxidation.International journal of molecular sciences · 2023Review
- ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden.Genome medicine · 2023Article
- Diverse and unselected adults with clinically relevant ACADS variants lack evidence of metabolic disease.Molecular genetics and metabolism · 2023Article
- Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.Metabolites · 2022Article
- Variants in the ethylmalonyl-CoA decarboxylase (ECHDC1) gene: a novel player in ethylmalonic aciduria?Journal of inherited metabolic disease · 2021Article
- Endotypes of primary osteoarthritis identified by plasma metabolomics analysis.Rheumatology (Oxford, England) · 2021Article
- A cross-platform approach identifies genetic regulators of human metabolism and health.Nature genetics · 2021Article
- Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience.Molecular genetics and metabolism reports · 2020Article
- A recurrent de novoCold Spring Harbor molecular case studies · 2020Review
- Article
- New Ratios for Performance Improvement for Identifying Acyl-CoA Dehydrogenase Deficiencies in Expanded Newborn Screening: A Retrospective Study.Frontiers in genetics · 2019Article
- Fatty acid oxidation disorders.Annals of translational medicine · 2018Review
- Lipid Myopathies.Journal of clinical medicine · 2018Review
- Improving the diagnosis of cobalamin and related defects by genomic analysis, plus functional and structural assessment of novel variants.Orphanet journal of rare diseases · 2018Article
- Clinical and genetic characteristics of patients with fatty acid oxidation disorders identified by newborn screening.BMC pediatrics · 2018Article
- Short-chain acyl-CoA dehydrogenase deficiency: from gene to cell pathology and possible disease mechanisms.Journal of inherited metabolic disease · 2017Review
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Authors and funding
20 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an inherited disorder of mitochondrial fatty acid oxidation associated with variations in the ACADS gene and variable clinical symptoms. In addition to rare ACADS inactivating variations, two common variations, c.511C > T (p.Arg171Trp) and c.625G > A (p.Gly209Ser), have been identified in patients, but these are also present in up to 14% of normal populations leading to questions of their clinical relevance. The common variant alleles encode proteins with nearly normal enzymatic activity at physiological conditions in vitro. SCAD enzyme function, however, is impaired at increased temperature and the tendency to misfold increases under conditions of cellular stress. The present study examines misfolding of variant SCAD proteins identified in patients with SCAD deficiency. Analysis of the ACADS gene in 114 patients revealed 29 variations, 26 missense, one start codon, and two stop codon variations. In vitro import studies of variant SCAD proteins in isolated mitochondria from SCAD deficient (SCAD-/-) mice demonstrated an increased tendency of the abnormal proteins to misfold and aggregate compared to the wild-type, a phenomenon that often leads to gain-of-function cellular phenotypes. However, no correlation was found between the clinical phenotype and the degree of SCAD dysfunction. We propose that SCAD deficiency should be considered as a disorder of protein folding that can lead to clinical disease in combination with other genetic and environmental factors.
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