| Summary: | <p>Abstract</p> <p>Background</p> <p>Mice with a deleted <it>Gpihbp1 </it>gene encoding glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) develop severe chylomicronemia. We screened the coding regions of the human homologue – <it>GPIHBP1 </it>– from the genomic DNA of 160 unrelated adults with fasting chylomicronemia and plasma triglycerides >10 mmol/L, each of whom had normal sequence of the <it>LPL </it>and <it>APOC2 </it>genes.</p> <p>Results</p> <p>One patient with severe type 5 hyperlipoproteinemia (MIM 144650), fasting chylomicronemia and relapsing pancreatitis resistant to standard therapy was found to be homozygous for a novel <it>GPIHBP1 </it>missense variant, namely G56R. This mutation was absent from the genomes of 600 control subjects and 610 patients with hyperlipidemia. The <it>GPIHBP1 </it>G56 residue has been conserved throughout evolution and the G56R mutation was predicted to have compromised function. Her homozygous brother also had refractory chylomicronemia and relapsing pancreatitis together with early coronary heart disease. G56R heterozygotes in the family had fasting mild hypertriglyceridemia.</p> <p>Conclusion</p> <p>Thus, a very rare <it>GPIHBP1 </it>missense mutation appears to be associated with severe hypertriglyceridemia and chylomicronemia.</p>
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