title: Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis.
abstract: BACKGROUND
  Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) has been demonstrated to be essential for the in vivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations of GPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients.
  
  
  METHODS
  Two unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1.
  
  
  RESULTS
  The 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile).
  
  
  CONCLUSIONS
  In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia.
authors.affiliation: Department of Medicine and Dermatology, Lipids and Atherosclerosis Laboratory, CIMES, University of Málaga, Málaga, Spain. Electronic address: mariza@uma.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Ariza
authors.affiliation: Department of Internal Medicine, La Paz University Hospital, Madrid, Spain.
authors.forename: Pedro Luis
authors.initials: PL
authors.lastname: Martínez-Hernández
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.
authors.forename: Daiana
authors.initials: D
authors.lastname: Ibarretxe
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rabacchi
authors.affiliation: Department of Medicine and Dermatology, Lipids and Atherosclerosis Laboratory, CIMES, University of Málaga, Málaga, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Rioja
authors.affiliation: Department of Biochemistry, La Paz University Hospital, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grande-Aragón
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Plana
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.affiliation: Department of Medical Biosciences, Physiological Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia Modena, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.affiliation: Department of Medicine and Dermatology, Lipids and Atherosclerosis Laboratory, CIMES, University of Málaga, Málaga, Spain; Internal Medicine Unit, Virgen de la Victoria University Hospital, Málaga, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Valdivielso
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010195:Pancreatitis / Q000150:complications / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics*; D012008:Recurrence; D055815:Young Adult
chemical_list: C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein
keywords: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1); Lipoprotein lipase activity; Recurrent pancreatitis; Severe hypertriglyceridemia