Deletion of GPIHBP1 causing severe chylomicronemia.
Lipoprotein lipase (LPL) is a hydrolase that cleaves circulating triglycerides to release fatty acids to the surrounding tissues. The enzyme is synthesized in parenchymal cells and is transported to its site of action on the capillary endothelium by glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Inactivating mutations in LPL; in its cofactor, apolipoprotein (Apo) C2; or in GPIHBP1 cause severe hypertriglyceridemia. Here we describe an individual with complete deficiency of GPIHBP1. The proband was an Asian Indian boy who had severe chylomicronemia at 2 months of age. Array-based copy-number analysis of his genomic DNA revealed homozygosity for a 17.5-kb deletion that included GPIHBP1. A 44-year-old aunt with a history of hypertriglyceridemia and pancreatitis was also homozygous for the deletion. A bolus of intravenously administered heparin caused a rapid increase in circulating LPL and decreased plasma triglyceride levels in control individuals but not in two GPIHBP1-deficient patients. Thus, short-term treatment with heparin failed to attenuate the hypertriglyceridemia in patients with GPIHBP1 deficiency. The increasing resolution of copy number microarrays and their widespread adoption for routine cytogenetic analysis is likely to reveal a greater role for submicroscopic deletions in Mendelian conditions. We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1.
Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Jonathan J
JJ
Rios
Savitha
S
Shastry
Juan
J
Jasso
Natalie
N
Hauser
Abhimanyu
A
Garg
André
A
Bensadoun
Jonathan C
JC
Cohen
Helen H
HH
Hobbs
D000328:Adult; D053304:Apolipoprotein C-II / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002914:Chylomicrons / Q000737:chemistry*; D003582:Cytogenetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006493:Heparin / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics*; D007223:Infant; D008071:Lipoprotein Lipase / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018110:Receptors, Lipoprotein
D053304:Apolipoprotein C-II; D002352:Carrier Proteins; D002914:Chylomicrons; C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein; D006493:Heparin; D008071:Lipoprotein Lipase