title: FH-Sydney 1 and 2: two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene detected by heteroduplex formation.
abstract: We report two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene that lead to familial hypercholesterolemia in separate lineages. The lesions, FH-Sydney 1 and FH-Sydney 2, were detected by a modified heteroduplex analysis of exon-specific polymerase chain reaction (PCR) amplified DNA, and characterized at the molecular level by sequencing. Restriction enzyme digestion of PCR amplified DNA confirmed the presence of the mutant alleles in affected family members and their absence in nonaffected family members in both lineages. FH-Sydney 1 is a 4-bp duplication at position 1373, while FH-Sydney 2 is a 2-bp deletion at position 1478. The predicted result of both mutations is the premature truncation of the receptor at stop codons generated downstream of the mutations. Neither mutation was detected in a survey of 54 unrelated familial hypercholesterolemia patients.
authors.affiliation: Human Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra.
authors.forename: J A
authors.initials: JA
authors.lastname: Cavanaugh
authors.forename: S
authors.initials: S
authors.lastname: Easteal
authors.forename: L A
authors.initials: LA
authors.lastname: Simons
authors.forename: D W
authors.initials: DW
authors.lastname: Thomas
authors.forename: S W
authors.initials: SW
authors.lastname: Serjeantson
mesh_terms: D001483:Base Sequence; D005091:Exons; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D009692:Nucleic Acid Heteroduplexes; D011973:Receptors, LDL