Letter abstract
Nature Genetics 39, 1483 - 1487 (2007)
Published online: 11 November 2007 | doi:10.1038/ng.2007.24
Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia
Miklós Péterfy1,2, Osnat Ben-Zeev1,2, Hui Z Mao1,2,10, Daphna Weissglas-Volkov3, Bradley E Aouizerat4,5, Clive R Pullinger4,9, Philip H Frost6, John P Kane6,7,9, Mary J Malloy6,8,9, Karen Reue2,3, Päivi Pajukanta3 & Mark H Doolittle1,2
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity1, 2, 3. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis4, 5, 6. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL)7, 8, 9, caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER)10. Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia4, 11, 12.
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
- VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California 94143, USA.
- Institute for Human Genetics, University of California, San Francisco, California 94143, USA.
- Department of Medicine, University of California, San Francisco, California 94143, USA.
- Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA.
- Pediatrics Research Institute, University of California, San Francisco, California 94143, USA.
- Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
- Present address: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, USA.
Correspondence to: Miklós Péterfy1,2 e-mail: mpeterfy@ucla.edu
Correspondence to: Mark H Doolittle1,2 e-mail: markdool@ucla.edu
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