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Accelerated epigenetic aging and DNA methylation alterations in Berardinelli–Seip congenital lipodystrophy

journal contribution
submitted on 2024-02-11, 09:14 and posted on 2024-02-11, 09:15 authored by Abeer Qannan, Yosra Bejaoui, Mahmoud Izadi, Noha A Yousri, Aleem Razzaq, Colette Christiansen, George M Martin, Jordana T Bell, Steve Horvath, Junko Oshima, Andre Megarbane, Johan Ericsson, Ehsan Pourkarimi, Nady El Hajj

Berardinelli–Seip congenital lipodystrophy type 2 (CGL2) is a very rare human genetic disorder with potential significance to the understanding of the pathobiology of aging. CGL2 patients display characteristic progeroid features and suffer from type 2 diabetes, insulin resistance and fatty liver. In this study, we profiled genome-wide DNA methylation levels in CGL2 patients with BSCL2 mutations to study epigenetic age acceleration and DNA methylation alterations. This analysis revealed significant age acceleration in blood DNA of CGL2 patients using both first- and second-generation epigenetic clocks. We also observed a shortened lifespan of Caenorhabditis elegans following knockdown of the BSCL2 homolog seip-1 on a daf-16/forkhead box, class O mutant background. DNA methylation analysis revealed significant differentially methylated sites enriched for lyase activity, kinase regulator activity, protein kinase regulator activity and kinase activator activity. We could also observe significant hypomethylation in the promoter of the dual specificity phosphatase 22 gene when comparing CGL2 patients versus controls. We conclude that in line with the observed progeroid features, CGL2 patients exhibit significant epigenetic age acceleration and DNA methylation alterations that might affect pathways/genes of potential relevance to the disease.

Other Information

Published in: Human Molecular Genetics
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Open Access funding provided by the Qatar National Library.



  • English


Oxford University Press

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • College of Science and Engineering - HBKU
  • Weill Cornell Medicine - Qatar

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