Familial Hypercholesterolemia in Utah Kindred with Novel R103W Mutations in Exon 4 of the LDL Receptor Gene

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

doi:10.1536/jhj.40.443

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

Author information

Harumi KATSUMATA
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
Yukiko NOBE
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 443-449

DOI https://doi.org/10.1536/jhj.40.443

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Abstract

Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein cholesterol levels early in childhood and very early coronary disease in both men and women. Previously published blood cholesterol criteria greatly under-diagnosed new cases of FH among members of known famillies with FH and over-diagnosed FH among participants of general population screening. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. 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 carry out molecular genetic diagnosis of the disease, we screened DNA samples for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein (LDL) receptor gene. Novel point mutations were identified in the proband: a C-to-T transversion at nucleotide position 369, causing substitution of Tryptophan for Arginine at codon 103 in exon 4 of the LDL receptor gene. The SSCP method was used to examine seven members of the family recruited for the diagnosis. This method helped to unequivocally diagnose only the proband as heterozygous for this particular LDL receptor mutation while excluding the remaining six individuals from carrier status with FH.

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