Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia.

Abstract

CONTEXT Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X). OBJECTIVE The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded. RESULTS The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and recurrent episodes of pancreatitis. The mutation causes a G>A substitution in exon 9 (c.1395G>A), leading to a premature stop codon (W464X). LPL activity and mass were reduced by 76 and 50%, respectively, compared with normolipidemic controls. The proband over the years has shown a good response to treatment. The proband's son, heterozygous for the W464X, shows normal plasma triglyceride levels. CONCLUSIONS We identified the second novel pathogenic mutation in LMF1 gene in a patient with severe hypertriglyceridemia. LPL deficiency in our patient was milder than in the carrier of the Y439X previously described.

DOI: 10.1210/jc.2009-0594

Cite this paper

@article{Cefal2009NovelLN, title={Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia.}, author={Angelo Baldassare Cefal{\`u} and Davide Noto and Maria Luisa Arpi and Fen Yin and Rossella Spina and H. Hilden and Carlo Maria Barbagallo and Antonio Carroccio and Patrizia Tarugi and Sebastiano Squatrito and Riccardo Vigneri and Marja-Riitta Taskinen and Mikl{\'o}s P{\'e}terfy and Maurizio Rocco Averna}, journal={The Journal of clinical endocrinology and metabolism}, year={2009}, volume={94 11}, pages={4584-90} }