title: Characterization of three mutations of the low density lipoprotein receptor gene in Italian patients with familial hypercholesterolemia.
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.
authors.affiliation: Istituto di Patologia Generale Università di Modena, Italia.
authors.forename: N
authors.initials: N
authors.lastname: Lelli
authors.forename: M
authors.initials: M
authors.lastname: Ghisellini
authors.forename: R
authors.initials: R
authors.lastname: Gualdi
authors.forename: R
authors.initials: R
authors.lastname: Tiozzo
authors.forename: S
authors.initials: S
authors.lastname: Calandra
authors.forename: A
authors.initials: A
authors.lastname: Gaddi
authors.forename: A
authors.initials: A
authors.lastname: Ciarrocchi
authors.forename: M
authors.initials: M
authors.lastname: Arca
authors.forename: S
authors.initials: S
authors.lastname: Fazio
authors.forename: D A
authors.initials: DA
authors.lastname: Coviello
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002872:Chromosome Deletion; D004247:DNA / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011973:Receptors, LDL / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D011973:Receptors, LDL; D004247:DNA