Nissen H, Hansen A B, Guldberg P, Petersen N E, Larsen M L, Haghfelt T, Kristiansen K, Hørder M
Department of Clinical Chemistry, Odense University Hospital, Denmark.
Atherosclerosis. 1994 Dec;111(2):209-15. doi: 10.1016/0021-9150(94)90095-7.
We performed a screening of exon 9 of the low density lipoprotein receptor (LDLR) gene in 14 Danish families with familial hypercholesterolemia (FH) using the denaturing gradient gel electrophoresis (DGGE) technique. In one of the probands from these families an abnormal band pattern in the gradient gel was detected. Subsequent DGGE analysis of the family of this index patient revealed that the DGGE pattern cosegregated with the disease in this family. Sequencing of the exon showed a deletion of a C in codon 424 of the LDLR gene resulting in a frame shift with the introduction of a stop codon 5 codons further downstream. The mutation is referred to as FH-Odense. The predicted truncated receptor protein consists of the 428 amino terminal amino acids. Consequently, the cytosolic and membrane spanning parts of the mature LDL receptor, which normally secure the receptor in the plasma membrane, are missing. The FH-Odense mutation results in severe premature coronary atherosclerosis as shown by the clinical expression in 5 generations of the affected family.
我们使用变性梯度凝胶电泳（DGGE）技术，对14个患有家族性高胆固醇血症（FH）的丹麦家庭的低密度脂蛋白受体（LDLR）基因外显子9进行了筛查。在这些家庭的一名先证者中，检测到梯度凝胶中出现异常条带模式。随后对该索引患者的家庭进行的DGGE分析显示，该家庭中DGGE模式与疾病共分离。外显子测序显示，LDLR基因第424密码子处的一个C缺失，导致移码，并在下游5个密码子处引入了一个终止密码子。该突变被称为FH-Odense。预测的截短受体蛋白由428个氨基末端氨基酸组成。因此，正常情况下将受体固定在质膜中的成熟LDL受体的胞质和跨膜部分缺失。如受影响家庭的5代临床表型所示，FH-Odense突变导致严重的早发性冠状动脉粥样硬化。
