A novel GPIHBP1 mutation related to familial chylomicronemia syndrome: A series of cases

Background and aims: GPIHBP1 is an accessory protein of lipoprotein lipase (LPL) essential for its functioning. Mutations in the GPIHBP1 gene cause a deficit in the action of LPL, leading to severe hypertriglyceridemia and increased risk for acute pancreatitis.

Methods: We describe twelve patients (nine women) with a novel homozygous mutation in intron 2 of the GPIHBP1 gene.

Results: All patients were from the Northeastern region of Brazil and presented the same homozygous variant located in a highly conserved 3' splicing acceptor site of the GPIHBP1 gene. This new variant was named c.182-1G > T, according to HGVS recommendations. We verified this new GPIHBP1 variant's effect by using the Human Splicing Finder (HSF) tool. This mutation changes the GPIHBP1 pre-mRNA processing and possibly causes the skipping of the exon 3 of the GPIHBP1 gene, affecting almost 50% of the cysteine-rich Lys6 GPIHBP1 domain. Patients presented with severe hypertriglyceridemia (2351 mg/dl [885-20600]) and low HDL (18 mg/dl [5-41). Four patients (33%) had a previous history of acute pancreatitis.

Conclusions: We describe a novel GPIHBP1 pathogenic intronic mutation of patients from the Northeast region of Brazil, suggesting the occurrence of a founder effect.