低密度脂蛋白受体基因中的两个新错义突变导致家族性高胆固醇血症。

Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia.

作者信息

Gundersen K E, Solberg K, Rødningen O K, Tonstad S, Ose L, Berg K, Leren T P

机构信息

Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway.

出版信息

Clin Genet. 1996 Feb;49(2):85-7. doi: 10.1111/j.1399-0004.1996.tb04333.x.

DOI:10.1111/j.1399-0004.1996.tb04333.x

PMID:8740918

Abstract

We have employed analysis of single-strand conformation polymorphisms to identify mutations in the low density lipoprotein receptor gene causing familial hypercholesterolemia. Two familial hypercholesterolemia heterozygotes had abnormal single-strand conformation polymorphism patterns of exons 4 and 8. DNA sequencing revealed that the abnormal pattern of exon 4 was due to heterozygosity (G/T) at nucleotide 502. Nucleotide 502 is the first base of codon 147, and the G->T mutation (D147Y) changes this codon from AspGAC to TyrUAC. The abnormal pattern of exon 8 was due to heterozygosity (A/G) at nucleotide 1097. Nucleotide 1097 is the second base of codon 345, and the A->G mutation (Q345R) changes this codon from GlnCAG to ArgCGG. Based upon screening of 437 unrelated familial hypercholesterolemia heterozygotes, both D147Y and Q345R account for about 0.5% of the mutations causing familial hypercholesterolemia in Norway.

摘要

我们采用单链构象多态性分析来鉴定导致家族性高胆固醇血症的低密度脂蛋白受体基因突变。两名家族性高胆固醇血症杂合子的外显子4和8呈现异常的单链构象多态性模式。DNA测序显示，外显子4的异常模式是由于核苷酸502处的杂合性（G/T）。核苷酸502是密码子147的第一个碱基，G→T突变（D147Y）使该密码子从AspGAC变为TyrUAC。外显子8的异常模式是由于核苷酸1097处的杂合性（A/G）。核苷酸1097是密码子345的第二个碱基，A→G突变（Q345R）使该密码子从GlnCAG变为ArgCGG。基于对437名无亲缘关系的家族性高胆固醇血症杂合子的筛查，在挪威，D147Y和Q345R这两种突变在导致家族性高胆固醇血症的突变中约占0.5%。