We systematically investigated the molecular defects resulting in primary lipoprotein lipase (LPL) deficiency in a Japanese male infant (hereafter called ‘the patient’) with severe fasting hypertriglyceridaemia (type I hyperlipoproteinaemia). The primary LPL deficiency was diagnosed on the basis of the findings that no LPL activity was detected in post-heparin plasma (PHP) and that the immunoreactive LPL mass in PHP was less than 2% of the control level. The patient was a compound heterozygote for a novel missense mutation (G̲568GA → A̲GA/Gly105 → Arg; G105R) in exon 3 and a missense mutation (GAC̲867→GAG̲/Asp204→Glu; D204E) in exon 5 of the LPL gene. The biological significance of both missense mutations was examined by an in vitro study of the expression of the mutant G105R LPL cDNA and D204E LPL cDNA in COS-1 cells. Both mutant LPLs were catalytically inactive and were barely released by heparin from the expressing COS-1 cells. These findings explain the failure to detect LPL activity and immunoreactive LPL mass in the patient's PHP. The G105R allele could be detected by digestion with the BsmAI restriction enzyme, and the D204E allele by digestion with HincII. The patient inherited the G105R allele from his mother and the D204E allele from his father. His parents were heterozygotes for the corresponding mutant allele, but normolipidaemic. The novel G105R missense mutation could not be detected by conventional analysis of single-strand conformation polymorphism, but it was identified by extensive sequencing of the entire exons and their flanking regions in the LPL gene.
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November 21 2000
A compound heterozygote for a novel missense mutation (G105R) in exon 3 and a missense mutation (D204E) in exon 5 of the lipoprotein lipase gene in a Japanese infant with hyperchylomicronaemia
Yasuyuki IKEDA;
*Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan
Correspondence: Dr Yasuyuki Ikeda (e-mail [email protected]).
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Katsumi GOJI;
Katsumi GOJI
†Department of Endocrinology and Metabolism, Kobe Children's Hospital, Kobe, Hyogo 654-0081, Japan
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Atsuko TAKAGI
Atsuko TAKAGI
‡Department of Pharmacology, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan
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Publisher: Portland Press Ltd
Received:
May 18 2000
Revision Received:
July 24 2000
Accepted:
September 07 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (6): 569–578.
Article history
Received:
May 18 2000
Revision Received:
July 24 2000
Accepted:
September 07 2000
Citation
Yasuyuki IKEDA, Katsumi GOJI, Atsuko TAKAGI; A compound heterozygote for a novel missense mutation (G105R) in exon 3 and a missense mutation (D204E) in exon 5 of the lipoprotein lipase gene in a Japanese infant with hyperchylomicronaemia. Clin Sci (Lond) 1 December 2000; 99 (6): 569–578. doi: https://doi.org/10.1042/cs0990569
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