The Lebanese mutation as an important cause of familial hypercholesterolemia in Brazil

Familial hypercholesterolemia (FH) is a common autosomal disorder that affe cts about one in 500 individuals in most Western populations and is caused by a defect in the low-density-lipoprotein receptor (LDLr) gene. In this re port we determined the molecular basis of FH in 59 patients from 31 unrelat ed Brazilian families. All patients were screened for the Lebanese mutation , gross abnormalities of the LDLr gene, and the point mutation in the codon 3500 of the apolipoprotein B-100 gene. None of the 59 patients presented t he apoB-3500 mutation, suggesting that familial defective ApoB-100 (FDB) is not a major cause of inherited hypercholesterolemia in Brazil. A novel 4-k b deletion in the LDLr gene, spanning from intron 12 to intron 14, was char acterized in one family. Both 5' and 3' breakpoint regions were located wit hin Alu repetitive sequences, which are probably involved in the crossing o ver that generated this rearrangement. The Lebanese mutation was detected i n 9 of the 31 families, always associated with Arab ancestry. Two different LDLr gene haplotypes were demonstrated in association with the Lebanese mu tation. Our results suggest the importance of the Lebanese mutation as a ca use of FH in Brazil and by analogy the same feature may be expected in othe r countries with a large Arab population, such as North American and Wester n European countries.