Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia.
BACKGROUND
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.
Cefalù
Angelo B
AB
Department of Clinical Medicine and Emerging Diseases, University of Palermo, 90127 Palermo, Italy.
Noto
Davide
D
Arpi
Maria Luisa
ML
Yin
Fen
F
Spina
Rossella
R
Hilden
Hannele
H
Barbagallo
Carlo M
CM
Carroccio
Antonio
A
Tarugi
Patrizia
P
Squatrito
Sebastiano
S
Vigneri
Riccardo
R
Taskinen
Marja-Riitta
MR
Péterfy
Miklós
M
Averna
Maurizio R
MR
D000328:Adult; D001483:Base Sequence; D018389:Codon, Nonsense; D015248:Gemfibrozil / Q000627:therapeutic use; D014644:Genetic Variation; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D014280:Triglycerides / Q000097:blood
D018389:Codon, Nonsense; D000960:Hypolipidemic Agents; D014280:Triglycerides; D008071:Lipoprotein Lipase; D015248:Gemfibrozil