A naturally occurring mutation at the second base of codon asparagine 43 in 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 and cholesterol levels were 1258 mg/dl and 138 mg/dl, respectively. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the patient were 0.00 mumol/ml/h (normal range: 5.51 +/- 1.12) and 23 ng/ml (normal range: 220 +/- 42), respectively. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a A-->G transition at nucleotide position 383, resulting in an amino acid substitution of Ser for Asn43, which is believed to be an N-linked 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.
Kobayashi
J
J
Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892.
Inadera
H
H
Fujita
Y
Y
Talley
G
G
Morisaki
N
N
Yoshida
S
S
Saito
Y
Y
Fojo
S S
SS
Brewer
H B
HB
D000328:Adult; D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics*; D001483:Base Sequence; D003062:Codon; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D006031:Glycosylation; D006493:Heparin; D006801:Humans; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012694:Serine / Q000235:genetics
D003062:Codon; D018076:DNA, Complementary; D012694:Serine; D001216:Asparagine; D006493:Heparin; D008071:Lipoprotein Lipase