Abstract
In the course of investigations of familial coronary artery disease in Hokkaido, the northland of Japan, we identified 13 families affected by familial hypercholesterolemia. Among them, we identified eight novel mutations of the low-density lipoprotein (LDL) receptor gene, four of which caused frameshifts: (1) a 7-bp deletion at nucleotide (nt) 578–584 (codon 172–174, exon 4); (2) a 14-bp insertion at 682 nt (codon 207–208, exon 4); (3) a 49-bp deletion at nt 943–991 (codon 294–310, exon 7); and (4) a one-base insertion of C to a stretch of C3 at nucleotides 1687–1689 or codon 542. The others included (5) a T-to-C transition at nt 1072 causing substitution of Cys for Arg at codon 337 (C337R, exon 8); (6) a splice-site G-to-T substitution in intron 11; (7) a splice-site G-to-C substitution in intron 11; and (8) a G-to-T transition at nt 1731 causing substitution of Trp for Cys at codon 556 (W556C, exon 12). To disclose the functional consequences of novel mutations, we characterized each of these mutations by two assays in peripheral lymphocytes, i.e., uptake of fluorescently labeled LDL by LDL receptors, and measurement of cell surface-bound LDL receptor protein using specific monoclonal antibody against LDL receptor.
Article PDF
Author information
Authors and Affiliations
Additional information
Received: September 27, 2001 / Accepted: November 12, 2001
Rights and permissions
About this article
Cite this article
Hattori, H., Hirayama, T., Nobe, Y. et al. Eight novel mutations and functional impairments of the LDL receptor in familial hypercholesterolemia in the north of Japan. J Hum Genet 47, 80–87 (2002). https://doi.org/10.1007/s100380200005
Issue Date:
DOI: https://doi.org/10.1007/s100380200005
This article is cited by
-
Association of single nucleotide polymorphisms in the promoter region of the pro-opiomelanocortin gene (POMC) with low bone mineral density in adult women
Journal of Human Genetics (2005)
-
Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia
Journal of Human Genetics (2005)
-
Hypercholesterolemia associated with splice-junction variation of inter-α-trypsin inhibitor heavy chain 4 (ITIH4) gene
Journal of Human Genetics (2004)
-
Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred
Journal of Human Genetics (2004)
-
Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients
Journal of Human Genetics (2004)