Compound heterozygosity for a known and a novel defect in the lipoprotein lipase gene (Asp250->Asn; Ser251->Cys) resulting in lipoprotein lipase (LPL) deficiency

Two missense mutations in exon 6 of the LPL gene were identified on separate alleles in a Dutch patient with lipoprotein lipase (LPL) deficiency. The first mutation is a G(1003) --> A transition resulting in a D250N mutation, which has been shown previously to result in a catalytically defective protein in patients of French-Canadian ancestry. The second mutation, a C to G transition at nucleotide 1007, predicts a S251C residue change in the highly conserved region of LPL surrounding the loop structure that covers the catalytic triad. This mutation constitutes a novel defect among LPL gene mutations reported so far. Site-directed mutagenesis experiments provide in-vitro evidence for the complete loss of LPL activity resulting from this latter missense mutation. The G(1003) --> A nucleotide substitution underlying the Asp(250) mutation deletes a TaqI endonuclease recognition site and the C-1007 --> G change that leads to the S251C alteration abolishes a HinfI recognition site. This will facilitate rapid screening for these mutations in LPL-deficient patients.