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 se parate alleles in a Dutch patient with lipoprotein lipase (LPL) defici ency. The first mutation is a G(1003) --> A transition resulting in a D250N mutation, which has been shown previously to result in a catalyt ically defective protein in patients of French-Canadian ancestry. The second mutation, a C to G transition at nucleotide 1007, predicts a S2 51C residue change in the highly conserved region of LPL surrounding t he loop structure that covers the catalytic triad. This mutation const itutes a novel defect among LPL gene mutations reported so far. Site-d irected mutagenesis experiments provide in-vitro evidence for the comp lete loss of LPL activity resulting from this latter missense mutation . The G(1003) --> A nucleotide substitution underlying the Asp(250) mu tation deletes a TaqI endonuclease recognition site and the C-1007 --> G change that leads to the S251C alteration abolishes a HinfI recogni tion site. This will facilitate rapid screening for these mutations in LPL-deficient patients.