ILE(225)THR LOOP MUTATION IN THE LIPOPROTEIN-LIPASE (LPL) GENE IS A DE-NOVO EVENT

Mutations in the lipoprotein lipase (LPL) gene are the most important cause of familial chylomicronemia with over 70 mutations being recorde d to date. Thus far de novo mutations have not been described. Here we report on the molecular analysis of the family of a patient previousl y reported to be LPL deficient on the basis of compound heterozygosity for the Arg(243)His and Ile(225)Thr mutations, the latter being the f irst and only mutation identified in the loop region of LPL, Both pare nts of the propositus were screened for the presence of these two muta tions to confirm their status as obligate heterozygotes and to determi ne the mutation allocation. Although paternal inheritance of the Arg24 3His allele could be established, maternal DNA did not show carrier st atus for the Ile225Thr substitution, An examination of maternity, usin g LPL restriction fragment length polymorphisms four polymorphic CA re peats and ApoE genotypes, was consistent with. correct biological pare ntage for the propositus, Therefore, we conclude that the IIe(225)Thr mutation constitutes a de novo event, the first to be reported in the LPL gene.