BACKGROUND: Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors and is most often attributable to mutations in the lipoprotein lipase (LPL) gene. OBJECTIVES: The aim of this study was to identify rare mutations in the LPL gene causing severe hypertriglyceridemia. METHODS: A Chinese infant who presented classical features of severe hypertriglyceridemia recruited for DNA sequencing of the LPL gene. The pathogenicity grade of the variants was defined based on the prediction of pathogenicity using in silico prediction tools. Review some studies to understand the molecular mechanisms underlying the severe hypertriglyceridemia. RESULTS: We identified a rare mutation in the LPL gene causing severe hypertriglyceridemia: a nucleotide substitution (c.836T>G) resulting in a leucine to arginine substitution at position 279 of the protein (p.Leu279Arg).The pathogenicity of the variant was predicted by in silico analysis using PolyPhen2 and SIFT prediction programs, which indicated that mutation p.Leu279Arg is probably harmful. We have also reviewed published studies concerning the molecular mechanisms underlying severe hypertriglyceridemia. A missense mutation in the 6 exon of the LPL gene is reportedly associated with LPL deficiency. CONCLUSIONS: We have here identified a rare pathogenic mutation in the LPL gene in a Chinese infant with severe hypertriglyceridemia.
BACKGROUND: Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors and is most often attributable to mutations in the lipoprotein lipase (LPL) gene. OBJECTIVES: The aim of this study was to identify rare mutations in the LPL gene causing severe hypertriglyceridemia. METHODS: A Chinese infant who presented classical features of severe hypertriglyceridemia recruited for DNA sequencing of the LPL gene. The pathogenicity grade of the variants was defined based on the prediction of pathogenicity using in silico prediction tools. Review some studies to understand the molecular mechanisms underlying the severe hypertriglyceridemia. RESULTS: We identified a rare mutation in the LPL gene causing severe hypertriglyceridemia: a nucleotide substitution (c.836T>G) resulting in a leucine to arginine substitution at position 279 of the protein (p.Leu279Arg).The pathogenicity of the variant was predicted by in silico analysis using PolyPhen2 and SIFT prediction programs, which indicated that mutation p.Leu279Arg is probably harmful. We have also reviewed published studies concerning the molecular mechanisms underlying severe hypertriglyceridemia. A missense mutation in the 6 exon of the LPL gene is reportedly associated with LPL deficiency. CONCLUSIONS: We have here identified a rare pathogenic mutation in the LPL gene in a Chinese infant with severe hypertriglyceridemia.
Authors: Y Saika; N Sakai; M Takahashi; T Maruyama; S Kihara; N Ouchi; M Ishigami; H Hiraoka; T Nakamura; S Yamashita; Y Matsuzawa Journal: Eur J Clin Invest Date: 2003-03 Impact factor: 4.686
Authors: Daniela S Gerhard; Lukas Wagner; Elise A Feingold; Carolyn M Shenmen; Lynette H Grouse; Greg Schuler; Steven L Klein; Susan Old; Rebekah Rasooly; Peter Good; Mark Guyer; Allison M Peck; Jeffery G Derge; David Lipman; Francis S Collins; Wonhee Jang; Steven Sherry; Mike Feolo; Leonie Misquitta; Eduardo Lee; Kirill Rotmistrovsky; Susan F Greenhut; Carl F Schaefer; Kenneth Buetow; Tom I Bonner; David Haussler; Jim Kent; Mark Kiekhaus; Terry Furey; Michael Brent; Christa Prange; Kirsten Schreiber; Nicole Shapiro; Narayan K Bhat; Ralph F Hopkins; Florence Hsie; Tom Driscoll; M Bento Soares; Tom L Casavant; Todd E Scheetz; Michael J Brown-stein; Ted B Usdin; Shiraki Toshiyuki; Piero Carninci; Yulan Piao; Dawood B Dudekula; Minoru S H Ko; Koichi Kawakami; Yutaka Suzuki; Sumio Sugano; C E Gruber; M R Smith; Blake Simmons; Troy Moore; Richard Waterman; Stephen L Johnson; Yijun Ruan; Chia Lin Wei; S Mathavan; Preethi H Gunaratne; Jiaqian Wu; Angela M Garcia; Stephen W Hulyk; Edwin Fuh; Ye Yuan; Anna Sneed; Carla Kowis; Anne Hodgson; Donna M Muzny; John McPherson; Richard A Gibbs; Jessica Fahey; Erin Helton; Mark Ketteman; Anuradha Madan; Stephanie Rodrigues; Amy Sanchez; Michelle Whiting; Anup Madari; Alice C Young; Keith D Wetherby; Steven J Granite; Peggy N Kwong; Charles P Brinkley; Russell L Pearson; Gerard G Bouffard; Robert W Blakesly; Eric D Green; Mark C Dickson; Alex C Rodriguez; Jane Grimwood; Jeremy Schmutz; Richard M Myers; Yaron S N Butterfield; Malachi Griffith; Obi L Griffith; Martin I Krzywinski; Nancy Liao; Ryan Morin; Ryan Morrin; Diana Palmquist; Anca S Petrescu; Ursula Skalska; Duane E Smailus; Jeff M Stott; Angelique Schnerch; Jacqueline E Schein; Steven J M Jones; Robert A Holt; Agnes Baross; Marco A Marra; Sandra Clifton; Kathryn A Makowski; Stephanie Bosak; Joel Malek Journal: Genome Res Date: 2004-10 Impact factor: 9.043
Authors: Anna M Bennet; Emanuele Di Angelantonio; Zheng Ye; Frances Wensley; Anette Dahlin; Anders Ahlbom; Bernard Keavney; Rory Collins; Björn Wiman; Ulf de Faire; John Danesh Journal: JAMA Date: 2007-09-19 Impact factor: 56.272