ArticleJournal of cellular and molecular medicine2009
The R439C mutation in LMNA causes lamin oligomerization and susceptibility to oxidative stress.
Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Metabolic Dysregulation in Laminopathies: Implications for Heart Failure and Cardiac Health.Current heart failure reports · 2026Review
- Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of functionNucleus (Austin, Tex.) · 2025Review
- Clinical and metabolic consequences of a historic pathogenic lamin A/C founder variant.Scientific reports · 2025Article
- The lamin A/C Ig-fold undergoes cell density-dependent changes that alter epitope binding.Nucleus (Austin, Tex.) · 2023Article
- Review
- Review
- Lamin A/C Mechanotransduction in Laminopathies.Cells · 2020Review
- Looking at New Unexpected Disease Targets inCells · 2020Article
- Assessment of fibroblast nuclear morphology aids interpretation of LMNA variants.European journal of human genetics : EJHG · 2019Article
- Modeling Skeletal Muscle Laminopathies Using Human Induced Pluripotent Stem Cells Carrying PathogenicFrontiers in physiology · 2018Article
- Laminopathy-causing lamin A mutations reconfigure lamina-associated domains and local spatial chromatin conformation.Nucleus (Austin, Tex.) · 2018Review
- Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives.Nucleus (Austin, Tex.) · 2018Review
- A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus.PloS one · 2017Article
- Nestin regulates proliferation and invasion of gastrointestinal stromal tumor cells by altering mitochondrial dynamics.Oncogene · 2016Article
- Fitting the pieces of the puzzle together: a case report of the Dunnigan-type of familial partial lipodystrophy in the adolescent girl.BMC pediatrics · 2016Article
- Myopathic lamin mutations cause reductive stress and activate the nrf2/keap-1 pathway.PLoS genetics · 2015Article
- New look at the role of progerin in skin aging.Przeglad menopauzalny = Menopause review · 2015Review
- Nuclear lamins and oxidative stress in cell proliferation and longevity.Advances in experimental medicine and biology · 2014Review
- Cytoplasmic localization of PML particles in laminopathies.Histochemistry and cell biology · 2013Article
- Inner nuclear membrane proteins: impact on human disease.Chromosoma · 2012Review
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dunnigan-type familial partial lipodystrophy (FPLD) is a laminopathy characterized by an aberrant fat distribution and a metabolic syndrome for which oxidative stress has recently been suggested as one of the disease-causing mechanisms. In a family affected with FPLD, we identified a heterozygous missense mutation c.1315C>T in the LMNA gene leading to the p.R439C substitution. Cultured patient fibroblasts do not show any prelamin A accumulation and reveal honeycomb-like lamin A/C formations in a significant percentage of nuclei. The mutation affects a region in the C-terminal globular domain of lamins A and C, different from the FPLD-related hot spot. Here, the introduction of an extra cysteine allows for the formation of disulphide-mediated lamin A/C oligomers. This oligomerization affects the interaction properties of the C-terminal domain with DNA as shown by gel retardation assays and causes a DNA-interaction pattern that is distinct from the classical R482W FPLD mutant. Particularly, whereas the R482W mutation decreases the binding efficiency of the C-terminal domain to DNA, the R439C mutation increases it. Electron spin resonance spectroscopy studies show significantly higher levels of reactive oxygen species (ROS) upon induction of oxidative stress in R439C patient fibroblasts compared to healthy controls. This increased sensitivity to oxidative stress seems independent of the oligomerization and enhanced DNA binding typical for R439C, as both the R439C and R482W mutants show a similar and significant increase in ROS upon induction of oxidative stress by H2O2.
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