Missense mutation W86R in exon 3 of the lipoprotein lipase gene in a boy with chylomicronemia

Clin Chim Acta. 2004 May;343(1-2):179-84. doi: 10.1016/j.cccn.2004.01.029.

Abstract

Background: Familial LPL deficiency is a rare inborn error of metabolism caused by mutational change within the LPL gene, which leads to massive hypertriglyceridemia.

Methods: The underlying molecular defect in a boy of Croatian descent was studied by SSCP analysis, DNA sequencing and finally confirmed by RFLP.

Results: DNA analysis showed the child to be a homozygote and his parents heterozygotes for TGG-->CGG change in codon 86 of the LPL gene, which leads to W86R amino acid substitution. DNA sequence analysis also showed a silent mutation in the third exon of father's DNA, V108V. Determination of some LPL gene polymorphisms showed the child and his parents to have HindIII/H+H+ and both S447 wild-type alleles, whereas for PvuII the parents had P(+)P- and the child P(+)P+ genotype.

Conclusions: In this case, W86R mutation was the reason for the production of nonfunctional enzyme and consequently triacylglycerol (TG) exceeding 15 mmol/l. This implies the risk of frequent episodes of acute pancreatitis. Decreased LPL activity leads to elevated triacylglycerol levels and reduced HDL-cholesterol, both risk factors for the development of coronary artery disease. LPL genotyping especially of young patients with hypertriglyceridemia is therefore necessary and justifiable.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Child, Preschool
  • Chylomicrons / blood*
  • Exons / genetics*
  • Female
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / genetics*
  • Lipoprotein Lipase / genetics*
  • Male
  • Mutation, Missense / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Tryptophan / genetics*

Substances

  • Chylomicrons
  • Tryptophan
  • Lipoprotein Lipase