Characterization of three mutations of the low density lipoprotein receptor gene in Italian patients with familial hypercholesterolemia.

Publisher Website
Google Scholar
Abstract
Three gross rearrangements of the low density lipoprotein receptor (LDL-R) gene were recognized during a survey of 23 unrelated Italian subjects with familial hypercholesterolemia (FH). Restriction endonuclease data were obtained by Southern blotting and hybridization with exon-specific probes. Proband FH-29 is heterozygous for a 4-kb deletion, which eliminates exons 13 and 14. This mutation is similar to that previously reported by other investigators in one Italian homozygous and two British and Canadian heterozygous patients. Proband FH-30 is homozygous for a 5.5-kb insertion caused by a duplication of exons 16 and 17 of the LDL-R gene. LDL-R mRNA isolated from skin fibroblasts of FH-30 was found to be larger than normal mRNA (5.6 versus 5.3 kb), in concordance with the insertion of the 236 nucleotides corresponding to exons 16 and 17. Proband FH-44 was found to have greater than 25-kb deletion, which eliminates the first six exons and the promoter region of the gene. This is the first example of a deletion that eliminates the promoter as well as the ligand-binding domain of the LDL-R gene. In the skin fibroblasts of this patient, the level of LDL-R mRNA was approximately half that found in control fibroblasts. We designate the new mutations found in FH-30 and FH-44 as FHviterbo and FHBologna-1, respectively, after the names of the Italian cities where the two patients were born.

This publication has 32 references indexed in Scilit: