Abstract: SA-PO0648
Does Laminopathy Include a Kidney Phenotype?
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Alsadhan, Abdulmajeed Abdullah, McMaster University, Hamilton, Ontario, Canada
- Gaheer, Pukhraj Singh, McMaster University, Hamilton, Ontario, Canada
- Lazarte, Julieta, McMaster University, Hamilton, Ontario, Canada
- Yeung, Hilary, Western University, London, Ontario, Canada
- Pigeyre, Marie, McMaster University, Hamilton, Ontario, Canada
- Hegele, Robert A., Western University, London, Ontario, Canada
- Lanktree, Matthew, McMaster University, Hamilton, Ontario, Canada
Background
Rare pathogenic variants in LMNA cause laminopathy phenotypes including muscular dystrophy, progeria, familial partial lipodystrophy, and cardiomyopathy. A kidney phenotype is not frequently associated with laminopathy.
Methods
We employed three approaches: 1) systematic search of the literature for reports of kidney disease associated with laminopathy, 2) an evaluation of kidney-related traits in a cohort of 29 patients with familial partial lipodystrophy, and 3) a phenome-wide association study searching for traits associated with rare LMNA variants in the United Kingdom Biobank (UKBB). We employed gene-based burden testing to aggregate the effects of rare LMNA variants in UKBB exome sequencing data (n = 373,812). Rare missense and loss-of-function LMNA variants were weighted using AlphaMissense. Variant location relative to a well studied nuclear localization signal was also evaluated. Logistic regression and Cox proportional hazards models were adjusted for age, sex, ancestry, and comorbidities.
Results
Ten patients with LMNA-associated kidney disease were found in the literature: 7 with focal segmental glomerulosclerosis, 2 with mesangioproliferative glomerulonephritis, and 1 without an established histological diagnosis. Among 29 patients with partial lipodystrophy (caused by LMNA R482Q and R482W), all had normal kidney function. Among 3,245 (0.87%) UKBB participants with a rare LMNA variant, there was an increased risk of AKI (hazard risk=1.55, 95% confidence interval (CI)=1.08-2.21, P=0.017) and albuminuria (odds ratio=3.58, 95% CI=1.55-8.27, P=0.003). Association with kidney traits was driven by variants upstream of the nuclear localization signal, an area classically associated with cardiomyopathy, in contrast to downstream variants associated with lipodystrophy.
Conclusion
Rare pathogenic LMNA variants—particularly those upstream of the nuclear localization signal —are associated with AKI and proteinuria.