A NATURALLY-OCCURRING MUTATION AT THE 2ND BASE OF CODON ASPARAGINE-43IN THE PROPOSED N-LINKED GLYCOSYLATION SITE OF HUMAN LIPOPROTEIN-LIPASE - IN-VIVO EVIDENCE THAT ASPARAGINE-43 IS ESSENTIAL FOR CATALYSIS AND SECRETION

The patient was a 20-year-old male. His fasting plasma triglyceride an d cholesterol levels were 1258 mg/dl and 138 mg/dl, respectively. The lipoprotein lipase(LPL) activity and mass from postheparin plasma of t he patient were 0.00 mu mol/ml/h (normal range: 5.51+/-1.12) and 23 ng /ml (normal range: 220+/-42), respectively. DNA sequence analysis of t he LPL gene from the patient revealed a homozymous nucleotide change: a A --> G transition at nucleotide position 383, resulting in an amino acid substitution of Ser for Asn(43), which is believed to be an N-li nked glycosylation site of the LPL mature protein. Expression studies of this mutant LPL cDNA produced an inactive LPL protein which was not secreted into the media. (C) 1994 academic Press, Inc.