Compound heterozygosity for a new (S259G) and a previously described (G188E) mutation in lipoprotein lipase (LpL) as a cause of chylomicronemia. Mutations in brief no. 183. Online

Abstract

Familial chylomicronemia is an autosomal recessive disease characterised by fasting triglyceridemia and an absence of lipoprotein lipase (LpL) activity in post-heparin plasma. The disease is a result of mutation in either the lipoprotein lipase (Lpl) gene or in the apoCII gene which codes for an essential co-factor. To date, over 80 mutations in the LpL gene have been reported. The proband, a 30 month old female, presented with fasting triglycerides of 3192 mg/dl, and no detectable LpL mass or activity in post-heparin plasma. Sequencing of all of the exons and exon/intron boundaries of the LpL gene showed that she was a compound heterozygote with G-A transitions in codon 188 (G188E:GGG to GAG) generating an avall restriction site and in codon 259 (S259G:AGT to GGT) generating a bssKI site. Restriction digests confirmed the mutations and determined the incidence within the family. The father (55%LPL activity), paternal aunt (82%) and paternal grandmother (29%) were all heterozygous for the S259G mutation whilst her sister (55%), mother (73%) and maternal grandfather (45%) were heterozygous for the G188E mutation. The maternal grandmother (114%) was unaffected.