Identification of a Pathogenic Mutation of the Lipase Maturation Factor 1 (LMF1) Gene Causing Recurrent Pancreatitis and Requiring Critical Care.

Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by extreme hypertriglyceridemia (>1000 mg/dL), recurrent pancreatitis, and lipoprotein lipase (LPL) deficiency. Mutations in the LMF1 gene, encoding a chaperone protein required for LPL maturation, can lead to combined lipase deficiency. This study reports a case of a 33-year-old Ecuadorian mestizo woman presenting with recurrent pancreatitis secondary to severe hypertriglyceridemia, in whom two LMF1 variants of uncertain significance (VUS) were identified.

Methods: Whole-exome sequencing (WES) was performed on the patient and her asymptomatic son using next-generation sequencing (NGS). Data analysis included computational pathogenicity predictors (REVEL, PolyPhen, SIFT, MutationTaster, etc.). Two LMF1 variants-c.1142C>T (p.Pro381Leu) and c.897G>A (p.Gln299Gln)-were identified. Their pathogenic potential was assessed based on allele frequency (gnomAD), bioinformatics predictions, and ACMG criteria.

Results: Both variants were classified as VUS, with c.897G>A predicted to affect splicing, potentially leading to loss of function. The c.1142C>T (p.Pro381Leu) variant, despite its low frequency, remains unclassified due to insufficient evidence. The patient's son carried one variant but was asymptomatic. The patient's phenotype suggested an intermediate form between monogenic and polygenic hypertriglyceridemia.

Conclusions: This is a new Ecuadorian report of LMF1-related hypertriglyceridemia, highlighting the need for functional studies to confirm pathogenicity. Given the classification of both variants as VUS, further research is required to elucidate their clinical significance. This case underscores the necessity of a combined genetic and biochemical approach for diagnosing and managing severe hypertriglyceridemia.