Kotze M J, Thiart R, Loubser O, de Villiers J N, Santos M, Vargas M A, Peeters A V
Department of Human Genetics, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
Hum Genet. 1996 Oct;98(4):476-8. doi: 10.1007/s004390050242.
Mutation analysis of the low density lipoprotein receptor (LDLR) gene revealed a novel 8-bp duplication after nucleotide 681 in a Costa Rican patient with familial hypercholesterolaemia. The frameshift caused by this mutation results in a premature termination codon in the EGF precursor homology domain of the mature LDLR, whereby a truncated protein of the first 206 residues with an additional 39 abnormal residues would be created. The insertion overlaps with previously described duplications of 18 bp and 21 bp, thus revealing an insertional hotspot in exon 4 of the LDLR gene. We propose that the structural features of this region of the LDLR gene contribute significantly to genetic instability and the subsequent DNA duplication via an endogenous sequence-directed mechanism of mutagenesis.
对一名患有家族性高胆固醇血症的哥斯达黎加患者的低密度脂蛋白受体（LDLR）基因进行突变分析，发现在核苷酸681之后有一个新的8碱基对重复序列。该突变导致的移码在成熟LDLR的EGF前体同源结构域中产生一个提前终止密码子，从而产生一个由前206个残基和另外39个异常残基组成的截短蛋白。该插入序列与先前描述的18碱基对和21碱基对重复序列重叠，从而揭示了LDLR基因第4外显子中的一个插入热点。我们认为，LDLR基因这一区域的结构特征通过内源性序列定向诱变机制对遗传不稳定性和随后的DNA重复有显著贡献。
