Partial lipodystrophy, severe dyslipidaemia and insulin resistant diabetes as early signs of Werner syndrome

Isis Atallah, Dominique McCormick, Jean-Marc Good, Mohammed Barigou, Montserrat Fraga, Christine Sempoux, Andrea Superti-Furga, Robert K. Semple, Christel Tran

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Werner syndrome is a premature ageing disorder caused by biallelic variants in the WRN gene. WRN encodes a dual DNA helicase/exonuclease enzyme. Molecular diagnosis is commonly only made at a late disease stage in the third or fourth decade, when cardinal features have become apparent. We describe a 28 year-old woman who presented with early onset diabetes associated with partial lipodystrophy, severe dyslipidaemia and rapidly progressive liver fibrosis related to non-alcoholic steatohepatitis in the absence of progeroid features. Werner syndrome was diagnosed by trio exome analysis, which revealed compound heterozygous WRN mutations: the known variant c.1290_1293del (p.Asn430Lysfs*7) and the novel intronic splice site variant c.2732+5G>A. cDNA analysis demonstrated this to lead to in-frame skipping of exon 22, predicted to delete most of the zinc binding region of the helicase domain. We suggest that including the WRN gene in genetic analysis of early onset diabetes, lipodystrophy or dyslipidaemia would allow for the opportunity to diagnose some cases of Werner syndrome long before clinical criteria are met, thereby allowing early implementation of important primary prevention interventions.
Original languageEnglish
JournalJournal of clinical lipidology
Early online date19 Jun 2022
Publication statusE-pub ahead of print - 19 Jun 2022

Keywords / Materials (for Non-textual outputs)

  • Werner syndrome
  • diabetes
  • dyslipidaemia
  • partial lipodystrophy
  • WRN
  • liver steatosis
  • helicase
  • Exome


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