ArticlePloS one2015
A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- PPARγ Gene as a Possible Link between Acquired and Congenital Lipodystrophy and its Modulation by Dietary Fatty Acids.Nutrients · 2022Pooled it
- Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability.Nature communications · 2024Article
- Role of Na/K-ATPase α1 caveolin-binding motif in adipogenesis.American journal of physiology. Cell physiology · 2024Article
- Hereditary severe insulin resistance syndrome: Pathogenesis, pathophysiology, and clinical management.Genes & diseases · 2023Review
- The building blocks of caveolae revealed: caveolins finally take center stage.Biochemical Society transactions · 2023Article
- Caveolae Mechanotransduction at the Interface between Cytoskeleton and Extracellular Matrix.Cells · 2023Review
- A deep learning-based tool for the automated detection and analysis of caveolae in transmission electron microscopy images.Computational and structural biotechnology journal · 2023Article
- Interactions between Caveolin-1 polymorphism and Plant-based dietary index on metabolic and inflammatory markers among women with obesity.Scientific reports · 2022Article
- Review
- DNA repair-related genes and adipogenesis: Lessons from congenital lipodystrophies.Genetics and molecular biology · 2022Article
- A synonymous variant contributes to a rare Wiedemann-Rautenstrauch syndrome complicated with mild anemiaFrontiers in molecular neuroscience · 2022Article
- Mediation role of body fat distribution (FD) on the relationship between CAV1 rs3807992 polymorphism and metabolic syndrome in overweight and obese women.BMC medical genomics · 2021Article
- Structure and assembly of CAV1 8S complexes revealed by single particle electron microscopy.Science advances · 2020Article
- Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet.International journal of molecular sciences · 2020Article
- Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies.Human genetics · 2020Article
- Expression of a Human Caveolin-1 Mutation in Mice Drives Inflammatory and Metabolic Defect-Associated Pulmonary Arterial Hypertension.Frontiers in medicine · 2020Article
- Energy and Dynamics of Caveolae Trafficking.Frontiers in cell and developmental biology · 2020Review
- Hereditary Syndromes with Signs of Premature Aging.Deutsches Arzteblatt international · 2019Review
- Deletion of caveolin scaffolding domain alters cancer cell migration.Cell cycle (Georgetown, Tex.) · 2019Article
- Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations.Human genetics · 2018Article
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A 3-year-old female patient presenting with an unknown syndrome of a neonatal progeroid appearance, lipodystrophy, pulmonary hypertension, cutis marmorata, feeding disorder and failure to thrive was investigated by whole-genome sequencing. This revealed a de novo, heterozygous, frame-shift mutation in the Caveolin1 gene (CAV1) (p.Phe160X). Mutations in CAV1, encoding the main component of the caveolae in plasma membranes, cause Berardinelli-Seip congenital lipodystrophy type 3 (BSCL). Although BSCL is recessive, heterozygous carriers either show a reduced phenotype of partial lipodystrophy, pulmonary hypertension, or no phenotype. To investigate the pathogenic mechanisms underlying this syndrome in more depth, we performed next generation RNA sequencing of peripheral blood, which showed several dysregulated pathways in the patient that might be related to the phenotypic progeroid features (apoptosis, DNA repair/replication, mitochondrial). Secondly, we found a significant down-regulation of known Cav1 interaction partners, verifying the dysfunction of CAV1. Other known progeroid genes and lipodystrophy genes were also dysregulated. Next, western blotting of lysates of cultured fibroblasts showed that the patient shows a significantly decreased expression of wild-type CAV1 protein, demonstrating a loss-of-function mutation, though her phenotype is more severe that other heterozygotes with similar mutations. This phenotypic variety could be explained by differences in genetic background. Indications for this are supported by additional rare variants we found in AGPAT2 and LPIN1 lipodystrophy genes. CAV1, AGPAT2 and LPIN1 all play an important role in triacylglycerol (TAG) biosynthesis in adipose tissue, and the defective function in different parts of this pathway, though not all to the same extend, could contribute to a more severe lipoatrophic phenotype in this patient. In conclusion, we report, for the first time, an association of CAV1 dysfunction with a syndrome of severe premature aging and lipodystrophy. This may contribute to a better understanding of the aging process and pathogenic mechanisms that contribute to premature aging.
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