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An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia

Ekström, Ulf LU ; Abrahamson, Magnus LU ; Sveger, Tomas LU ; Lombardi, Paola and Nilsson-Ehle, Peter LU (1995) In Human Genetics 96(2). p.147-150
Abstract
Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused by defects in the low density lipoprotein receptor (LDLR) gene and is a well-documented risk factor for developing cardiovascular disease. The LDLR genes of five Swedish children with FH were examined in this study. Initial mutation screening was performed by denaturing gradient gel electrophoresis (DGGE) with enzymatically amplified exon-sized fragments, each containing a tailing GC-rich requence. The GC-clamped fragments had been synthesized with a restriction site adjacent to the intron-corresponding sequence to allow detachment of the clamps, thereby rendering the fragments suitable for subsequent analysis by single-strand conformation polymorphism (SSCP)... (More)
Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused by defects in the low density lipoprotein receptor (LDLR) gene and is a well-documented risk factor for developing cardiovascular disease. The LDLR genes of five Swedish children with FH were examined in this study. Initial mutation screening was performed by denaturing gradient gel electrophoresis (DGGE) with enzymatically amplified exon-sized fragments, each containing a tailing GC-rich requence. The GC-clamped fragments had been synthesized with a restriction site adjacent to the intron-corresponding sequence to allow detachment of the clamps, thereby rendering the fragments suitable for subsequent analysis by single-strand conformation polymorphism (SSCP) analysis of samples from patients with no DGGE-detectable mutations. In addition, all the LDLR genes of the patients were screened for large alterations by restriction fragment length polymorphism analysis. Following this strategy, seven different, potentially disease-causing mutations were detected in the five children with FH. Six of the alterations, five single-base substitutions and one dinucleotide deletion, have not previously been described. DGGE detected six of the mutations and SSCP the seventh. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Genetics
volume
96
issue
2
pages
147 - 150
publisher
Springer
external identifiers
  • pmid:7635461
  • scopus:0029059348
ISSN
1432-1203
DOI
10.1007/BF00207370
language
English
LU publication?
yes
id
d23fd94b-ff6e-41ff-b6a0-7e23dec45f8f (old id 1109026)
date added to LUP
2008-07-25 12:31:22
date last changed
2017-07-30 04:41:37
@article{d23fd94b-ff6e-41ff-b6a0-7e23dec45f8f,
  abstract     = {Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused by defects in the low density lipoprotein receptor (LDLR) gene and is a well-documented risk factor for developing cardiovascular disease. The LDLR genes of five Swedish children with FH were examined in this study. Initial mutation screening was performed by denaturing gradient gel electrophoresis (DGGE) with enzymatically amplified exon-sized fragments, each containing a tailing GC-rich requence. The GC-clamped fragments had been synthesized with a restriction site adjacent to the intron-corresponding sequence to allow detachment of the clamps, thereby rendering the fragments suitable for subsequent analysis by single-strand conformation polymorphism (SSCP) analysis of samples from patients with no DGGE-detectable mutations. In addition, all the LDLR genes of the patients were screened for large alterations by restriction fragment length polymorphism analysis. Following this strategy, seven different, potentially disease-causing mutations were detected in the five children with FH. Six of the alterations, five single-base substitutions and one dinucleotide deletion, have not previously been described. DGGE detected six of the mutations and SSCP the seventh.},
  author       = {Ekström, Ulf and Abrahamson, Magnus and Sveger, Tomas and Lombardi, Paola and Nilsson-Ehle, Peter},
  issn         = {1432-1203},
  language     = {eng},
  number       = {2},
  pages        = {147--150},
  publisher    = {Springer},
  series       = {Human Genetics},
  title        = {An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia},
  url          = {http://dx.doi.org/10.1007/BF00207370},
  volume       = {96},
  year         = {1995},
}