Familial chylomicronemia syndrome (FCS) is a rare monogenic disorder characterized by severe hypertriglyceridemia caused by pathogenic variants in genes involved in triglyceride metabolism. Glycosylph Show more
Familial chylomicronemia syndrome (FCS) is a rare monogenic disorder characterized by severe hypertriglyceridemia caused by pathogenic variants in genes involved in triglyceride metabolism. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of triglyceride-rich lipoproteins. We present 3 unrelated cases of FCS with a newly identified homozygous complex insertion-deletion variant in GPIHBP1, namely c.460₄₆₁delinsAAA, p.Ala154Lysfs*153. All 3 cases presented with severe hypertriglyceridemia, a high FCS clinical score, and significantly reduced lipoprotein lipase (LPL) activity (being 6.6 mUI the value corresponding to 20% of normal activity). These observations expand the spectrum of pathogenic GPIHBP1 variants in FCS. The identification of GPIHBP1 variant reinforces the causal link between GPIHBP1 mutations and LPL deficiency, as evidenced by diminished LPL activity, and further expands the genetic landscape of FCS. Show less