Novel PPARG mutation in multiple family members with chylomicronemia

Chylomicronemia is characterized by severe hypertriglyceridemia when chylomicrons persist in plasma despite a fasting state. The recessive monogenic form is due to homozygous or compound heterozygous loss-of-function mutations in the LPL gene or genes involved in the assembly, transport, or function of LPL, including APOC2, APOA5, GP1HBP1, and LMF1. The multifactorial form of chylomicronemia is due to both common small-effect variants and rare heterozygous large-effect variants in genes in which mutations are associated secondarily with hypertriglyceridemia. The combined inheritance of these variants increases susceptibility to chylomicronemia, and the number of hypertriglyceridemia-associated alleles carried by an individual represents a genetic or polygenic triglyceride risk score. Among these genes associated with hypertriglyceridemia is PPARG. PPARγ is a nuclear transcription factor encoded by the PPARG gene expressed predominantly in adipocytes that is involved in glucose, lipid, and adipose tissue metabolism. Known rare mutations and common polymorphisms in the PPARG genes are associated with a broad range of clinical phenotypes, including hypertriglyceridemia. Here, we present multiple family members with a novel heterozygous PPARG mutation that has not been previously reported.