Lipodystrophy - childhood onset

Gene: WRN

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 31 Dec 2025, 7:17 p.m. | Last Modified: 31 Dec 2025, 7:17 p.m.

Panel Version: 4.66

This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.

Created: 17 Jun 2024, 8:59 a.m. | Last Modified: 17 Jun 2024, 8:59 a.m.

Panel Version: 4.54

Comment on list classification: There is sufficient evidence (three unrelated cases) in support of the association of this gene to severe insulin resistance/ diabetes and partial lipodystrophy and hence can be promoted to green rating at the next GMS review.

Created: 3 Aug 2023, 9:03 a.m. | Last Modified: 3 Aug 2023, 9:03 a.m.

Panel Version: 4.12

PMID:22654791 - A homozygous variant (p.Arg732Xaa) in WRN gene has been identified in a 16-year-old female patient with a syndrome comprising short stature, severe insulin resistance, ptosis, and microcephaly.

PMID:23849162 - Biallelic WRN null variants (p.Gln748Xaa homozygous, and compound heterozygous p.Gln1257Xaa/ p.Met1329fs) were identified in two female patients who presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them also had diabetes.

PMID:35780059 - Compound heterozygous variants (c.1290_1293del/ p.Asn430Lysfs*7 & c.2732+5G>A) in WRN gene was identified in 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.

This gene has been associated with Werner syndrome in both OMIM (MIM #277700) and Gene2Phenotype.

Created: 3 Aug 2023, 9 a.m. | Last Modified: 3 Aug 2023, 9 a.m.

Panel Version: 4.9

This gene was added on recommendation of NHSE Genomic Medicine Service:
Premature insulin resistant diabetes is widely recognised as a complication of Werner's syndrome and lipoatrophy is commonly reported. Crucially - 3 independent pedigrees have now reported lipodystrophy and/or severe insulin resistance as presenting features of Werner's syndrome highlighting that this condition needs to be considered in the differential diagnosis of lipodystrophy (PMID: 22654791, 35780059, 23849162). It has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244).

Created: 2 Aug 2023, 11:35 a.m. | Last Modified: 2 Aug 2023, 7:22 p.m.

Panel Version: 4.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Werner's Syndrome, partial lipodystrophy, severe insulin resistance

Publications

• 22654791
• 23849162
• 27710244
• 35780059