Loss-of-function homozygous variant in LPL causes type I hyperlipoproteinemia and renal lipidosis

BackgroundLipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by hyperlipoproteinemia due to mutation.MethodsRenal biopsy was conducted confirm the etiological factor nephrotic syndrome a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, whole-exome sequencing were performed dyslipidemia genetic factor. Analysis three-dimensional protein structure vitro functional study verify variant pathogenicity.ResultsRenal presented numerous CD68 positive foam cells infiltrated glomeruli, immunoglobulin complement staining negative, electron microscopy revealed droplets cholesterol clefts cytoplasm cells. electrophoresis that patient fulfilled diagnostic criteria hyperlipoproteinemia. The ε3/ε3 genotype.Whole-exome (c.292G > A, p.A98T) homozygous α-helix instability reduced post-heparin activity but normal uptake capability compared wild-type variant.ConclusionsLPL pathogenic causes associated This provides adequate evidence causal relationship between lesions. However, further research needed better understand pathogenesis mechanism variant-related