Familial Hypercholesterolemia in Utah Kindred with Novel 2412-6 Ins G Mutations in Exon 17 of the LDL Receptor Gene

Yukiko NOBE; Mitsuru EMI; Harumi KATSUMATA; Toshiaki NAKAJIMA; Tsunenori HIRAYAMA; Lily L. WU; Susan H. STEPHENSON; Paul N. HOPKINS; Roger R. WILLIAMS

doi:10.1536/jhj.40.435

Yukiko NOBE, Mitsuru EMI, Harumi KATSUMATA, Toshiaki NAKAJIMA, Tsunenori HIRAYAMA, Lily L. WU, Susan H. STEPHENSON, Paul N. HOPKINS, Roger R. WILLIAMS

Author information

Yukiko NOBE
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan
Mitsuru EMI
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan
Harumi KATSUMATA
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan
Toshiaki NAKAJIMA
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan
Tsunenori HIRAYAMA
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan
Lily L. WU
Cardiovascular Genetics Research Clinic, University of Utah Medical School, Salt Lake City, UT, USA
Susan H. STEPHENSON
Cardiovascular Genetics Research Clinic, University of Utah Medical School, Salt Lake City, UT, USA
Paul N. HOPKINS
Cardiovascular Genetics Research Clinic, University of Utah Medical School, Salt Lake City, UT, USA
Roger R. WILLIAMS
Cardiovascular Genetics Research Clinic, University of Utah Medical School, Salt Lake City, UT, USA

Keywords: Hyperlipoproteinemia, Lipoproteins, LDL receptor, Familial hypercholesterolemia, Genetic diagnosis

JOURNAL FREE ACCESS

1999 Volume 40 Issue 4 Pages 435-441

DOI https://doi.org/10.1536/jhj.40.435

Details

Abstract

Familial hypercholesterolemia (FH) is a monogenic disorder associated with primary hypercholesterolemia. FH is characterized by autosomal co-dominant inheritance with strikingly elevated LDL-cholesterol, the presence of xanthoma and premature atherosclerosis. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To determine the genetic etiology of the lipoprotein abnormalities, we screened DNA samples from the family for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein receptor (LDLR) gene. Novel point mutations were identified in the proband: a one-base insertion of G to a five-G stretch at nucleotides 2412-6 (codons 783-785), causing a frameshift in exon 17 of the LDL receptor gene. The direct sequencing method was used to examine six members of the family recruited for the diagnosis. This method helped to unequivocally diagnose the five individuals as heterozygous for this particular LDL receptor mutation. This method also helped us to diagnose with FH, or to exclude from carrier status, three children between ages 6 and 11.

Corresponding author

Register with J-STAGE for free!