Luc Foubert

Assessment of French patients with LPL deficiency for French Canadian mutations.

Mutations in the LPL gene show high levels of allelic heterogeneity between and within different populations. Complete LPL deficiency has a very high prevalence in French Canadians, where only three missense mutations account for > 97% of cases, most consistent with founder mutations introduced early in Quebec by French immigrants. In order to determine whether these mutations were present in France, 12 unrelated French families with defined LPL deficiency were investigated for the presence of the mutations found in French Canadians. Of the 24 expected alleles, six (25%) represented mutations in French Canadians (Gly188Glu four alleles, Asp250Asn and Pro207Leu one allele each). Comparison of French Canadian and French alleles identified the same haplotype in all carriers of the Gly188Glu and of the Asp250Asn, suggesting a common origin. In contrast, the Pro207Leu occurred on different haplotypes in France and Quebec, compatible with a different ancestral origin.

A single Ser259Arg mutation in the gene for lipoprotein lipase causes chylomicronemia in Moroccans of Berber ancestry.

Lipoprotein lipase (LPL) is the rate‐limiting enzyme for the hydrolysis of triglyceride‐rich lipoproteins. Numerous LPL gene mutations have been described as a cause of familial chylomicronemia in various populations. In general, allelic heterogeneity is observed in LPL deficiency in different populations. However, a founder effect has been reported in certain populations, such as French Canadians. Although familial chylomicronemia is observed in Morocco, the molecular basis for the disease remains unknown. Here, we report two unrelated Moroccan families of Berber ancestry, ascertained independently in Holland and France. In both probands, familial chylomicronemia manifested in infancy and was complicated with acute pancreatitis at age 2 years. Both probands were homozygous for a Ser259Arg mutation, which results in the absence of LPL catalytic activity both in vivo and in vitro. In heterozygous relatives, a partial decrease in plasma LPL activity was observed, sometimes associated with combined hyperlipidemia. This mutation previously unreported in other populations segregated on an identical haplotype, rarely observed in Caucasians, in both families. Therefore, LPL deficiency is a cause of familial chylomicronemia in Morocco and may result from a founder effect in patients of Berber ancestry. Hum Mutat 10:179–185, 1997.