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

Andrés Fernando Montalvo; González Andrade, Fabricio; María José Molestina; Jhonny Manuel Carranza; Claudio Maldonado; Denise Battaglini; Jorge Luis Vélez-Paéz

doi:10.3390/jcm14061827

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

Journal

Journal of Clinical Medicine

ISSN

2077-0383

Date Issued

2025

Author(s)

Andrés Fernando Montalvo

González Andrade, Fabricio

Facultad de Ciencias de la Salud y Bienestar Humano

María José Molestina

Jhonny Manuel Carranza

Claudio Maldonado

Denise Battaglini

Jorge Luis Vélez-Paéz

Type

journal-article

DOI

10.3390/jcm14061827

URL

https://cris.indoamerica.edu.ec/handle/123456789/9299

Abstract

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.