Intronic mutations at splice junctions in the low-density lipoprotein receptor gene

Most of the low-density lipoprotein receptor (LDLR) gene mutations causing familial hypercholesterolemia (FH) have been identified in the coding regio n of the gene. We have screened 180 patients for disease-related gene defec ts and report the identification of three previously described (IVS3 + 1G-- >A, IVS9-1G-->A and IVS16 - 2A-->G) and two novel mutations (IVS2 + 1G-->A and IVS14 + 1G-->T) at splice junctions. Approximately 9% (38/404) of LDLR gene point mutations identified to date in FH patients occur in introns and may affect splicing. The severe consequences of these mutations make them an important target for the molecular analysis of FH. (C) 1999 Academic Pre ss.