Two novel frameshift mutations associated with the presence of direct repeats of the LDL receptor gene in familial hypercholesterolemia
- 1 October 1993
- journal article
- Published by Springer Nature in Human Genetics
- Vol. 92 (4) , 331-335
- https://doi.org/10.1007/bf01247329
Abstract
Two novel frameshift mutations were detected in the mutant LDL receptor genes responsible for familial hypercholesterolemia. One was a 5-bp insertion at codon 395 in exon 9, and the other was a one nucleotide deletion at codon 531 in exon 11. Both mutations alter the reading frame and consequently produce a premature stop codon in the region of the mature LDL receptor homologous to the epidermal growth factor (EGF) precursor. With regard to the mechanism responsible for the generation of these frameshift mutations, strand slipped mispairing mediated by short direct repeats is considered to be the most likely. The findings seem to support the hypothesis that a short direct repeat in DNA sequence can have a profound influence on the stability of a given gene and promote human gene mutations.Keywords
This publication has 17 references indexed in Scilit:
- The familial hypercholesterolemia (FH)-North Karelia mutation of the low density lipoprotein receptor gene deletes seven nucleotides of exon 6 and is a common cause of FH in Finland.Journal of Clinical Investigation, 1992
- Mechanisms of insertional mutagenesis in human genes causing genetic diseaseHuman Genetics, 1991
- DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemiaClinical Genetics, 1991
- Repetitive sequences involved in the recombination leading to deletion of exon 5 of the low‐density‐lipoprotein receptor gene in a patient with familial hypercholesterolemiaEuropean Journal of Biochemistry, 1991
- Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environmentHuman Genetics, 1991
- Common low-density lipoprotein receptor mutations in the French Canadian population.Journal of Clinical Investigation, 1990
- Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reactionGenomics, 1989
- Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA PolymeraseScience, 1988
- The human LDL receptor: A cysteine-rich protein with multiple Alu sequences in its mRNACell, 1984
- Radiographic determination of Achilles tendon xanthoma sizeMetabolism, 1969