van den Maagdenberg A M, de Knijff P, Stalenhoef A F, Gevers Leuven J A, Havekes L M, Frants R R
Department of Human Genetics, State University Leiden, The Netherlands.
Biochem Biophys Res Commun. 1989 Dec 15;165(2):851-7. doi: 10.1016/s0006-291x(89)80044-0.
The apolipoprotein E3-Leiden variant has been shown to be associated with familial dysbetalipoproteinemia (FD) in a dominant manner (Havekes et al., Hum Genet 1986;73:157-163). Applying the polymerase chain reaction technique, we have cloned and sequenced relevant parts of both APOE alleles of the original proband. In exon 4 of the E3-Leiden allele a partial gene duplication encompassing 21 nucleotides was found, leading to a tandem repeat of the codons 120-126 or 121-127. Using an E3-Leiden mutation specific oligonucleotide probe, the same mutation was found in two additional independently ascertained FD patients with an E3E3 phenotype based on isoelectric focusing. The E3-Leiden mutation will be useful in the elucidation of the etiology of dominantly inherited forms of FD.
载脂蛋白E3-莱顿变体已被证明以显性方式与家族性异常β脂蛋白血症（FD）相关（Havekes等人，《人类遗传学》1986年；73:157-163）。应用聚合酶链反应技术，我们对最初先证者的两个APOE等位基因的相关部分进行了克隆和测序。在E3-莱顿等位基因的第4外显子中发现了一个包含21个核苷酸的部分基因重复，导致密码子120-126或121-127串联重复。使用E3-莱顿突变特异性寡核苷酸探针，在另外两名基于等电聚焦确定为E3E3表型的独立确诊的FD患者中发现了相同的突变。E3-莱顿突变将有助于阐明显性遗传形式的FD的病因。
