Ile225Thr loop mutation in thelipoprotein lipase (LPL) gene is a de novo event

✍ Scribed by Henderson, Howard E.; Bijvoet, Saskia M.; Mannens, Marcel A.M.M.; Bruin, Taco; Erkelens, D. Willem; Hayden, Michael R.; Kastelein, Johannes J.P.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 22 KB
• Volume: 78
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19980724)78:4<313::aid-ajmg1>3.0.co;2-m

✦ Synopsis

Mutations in the lipoprotein lipase (LPL) gene are the most important cause of familial chylomicronemia with over 70 mutations being recorded to date. Thus far de novo mutations have not been described. Here we report on the molecular analysis of the family of a patient previously 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 first and only mutation identified in the loop region of LPL. Both parents of the propositus were screened for the presence of these two mutations to confirm their status as obligate heterozygotes and to determine the mutation allocation. Although paternal inheritance of the Arg 243 His allele could be established, maternal DNA did not show carrier status for the Ile 225 Thr substitution. An examination of maternity, using LPL restriction fragment length polymorphisms four polymorphic CA repeats and ApoE genotypes, was consistent with correct biological parentage for the propositus. Therefore, we conclude that the Ile 225 Thr mutation constitutes a de novo event, the first to be re-ported in the LPL gene. Am.