Two novel frameshift mutations in the low density lipoprotein receptor gene generated by endogenous sequence-directed mechanisms
Date
1995
Authors
Peeters A.V.
Van Gaal L.F.
Theart L.
Langenhoven E.
Kotze M.J.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
DNA samples from 60 unrelated Belgian hypercholesterolemic patients were subjected to heteroduplex analysis of exon 4 of the low density lipoprotein receptor (LDLR) gene. Aberrant mobility bands were detected in 2 patients and the underlying mutations were characterized by DNA sequence analysis. Both mutations, a 19-bp insertion at codon 141 and a 23-bp deletion at codon 168, produce premature stop codons in the highly conserved ligand binding domain of the mature LDLR. Sequence data indicated that mispairing between short direct repeats during DNA replication is the most probable mechanism by which these mutations could have arisen. Our observations are consistent with an endogenous sequence-directed mechanism of mutagenesis.
Description
Keywords
high density lipoprotein cholesterol, low density lipoprotein receptor, triacylglycerol, adult, aged, article, blood sampling, cholesterol blood level, codon, dna determination, dna replication, dna sequence, exon, familial hypercholesterolemia, female, frameshift mutation, human, human cell, ligand binding, major clinical study, male, mutagenesis, nucleotide sequence, priority journal, protein domain, school child, stop codon, Adolescent, Adult, Base Sequence, Child, Female, Frameshift Mutation, Human, Male, Middle Age, Molecular Sequence Data, Pedigree, Receptors, LDL, Repetitive Sequences, Nucleic Acid, Support, Non-U.S. Gov't
Citation
Human Genetics
96
4
96
4