Missense mutation W86R in exon 3 of the lipoprotein lipase gene in a boy with chylomicronemia.
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.
Pasalić
Daria
D
Department of Chemistry and Biochemistry, Zagreb University School of Medicine, Salata 3 HR-10000 Zagreb, Croatia. dmikacic@mef.hr
Jurcić
Zvonko
Z
Stipancić
Gordana
G
Ferencak
Goran
G
Leren
Trond P
TP
Djurovic
Srdjan
S
Stavljenić-Rukavina
Ana
A
D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D002914:Chylomicrons / Q000097:blood*; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014364:Tryptophan / Q000235:genetics*
D002914:Chylomicrons; D014364:Tryptophan; D008071:Lipoprotein Lipase