Maruyama T, Miyake Y, Tajima S, Funahashi T, Matsuzawa Y, Yamamoto A
Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka, Japan.
Eur J Biochem. 1995 Sep 15;232(3):700-5.
Familial hypercholesterolemia is a genetic disorder caused by mutations of the low-density-lipoprotein (LDL) receptor gene. We characterized the structures of LDL receptor mRNA transcripts in the fibroblasts of a homozygous patient carrying a single base substitution (T-->C) at the 5' splice donor site of intron 12 of the LDL receptor gene. We identified three aberrant transcripts as a consequence of intron-12 read-through, exon-12 skipping and utilization of a cryptic splice donor site. Only a point mutation at the 5' splice donor site caused the production of three alternatively spliced products. None of these transcripts produced a functional LDL receptor protein in this patient.
家族性高胆固醇血症是一种由低密度脂蛋白（LDL）受体基因突变引起的遗传性疾病。我们对一名纯合子患者成纤维细胞中LDL受体mRNA转录本的结构进行了表征，该患者在LDL受体基因第12内含子的5'剪接供体位点发生了单碱基替换（T→C）。我们鉴定出三种异常转录本，分别是由于第12内含子通读、第12外显子跳跃以及隐蔽剪接供体位点的利用导致的。仅5'剪接供体位点的一个点突变就导致了三种可变剪接产物的产生。在该患者中，这些转录本均未产生功能性的LDL受体蛋白。
