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

Details

Serval ID
serval:BIB_E5FCC361A247
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Partial lipodystrophy, severe dyslipidaemia and insulin resistant diabetes as early signs of Werner syndrome.
Journal
Journal of clinical lipidology
Author(s)
Atallah I., McCormick D., Good J.M., Barigou M., Fraga M., Sempoux C., Superti-Furga A., Semple R.K., Tran C.
ISSN
1933-2874 (Print)
ISSN-L
1876-4789
Publication state
Published
Issued date
19/06/2022
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Keywords
Diabetes, Dyslipidaemia, Exome, Helicase, Liver steatosis, Partial lipodystrophy, Werner syndrome
Pubmed
Open Access
Yes
Create date
05/07/2022 7:36
Last modification date
29/10/2022 5:40
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