Lipodystrophy - childhood onset
Gene: WRN
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
Gene: wrn has been classified as Amber List (Moderate Evidence).
Tag Q3_23_promote_green tag was added to gene: WRN. Tag Q3_23_NHS_review tag was added to gene: WRN.
Phenotypes for gene: WRN were changed from Werner's Syndrome, partial lipodystrophy, severe insulin resistance to Werner syndrome, OMIM:277700
Publications for gene: WRN were set to
gene: WRN was added gene: WRN was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WRN were set to Werner's Syndrome, partial lipodystrophy, severe insulin resistance