A novel point mutation in a splice acceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia: An unexpected absence of exon skipping

✍ Scribed by Takao Maruyama; Yasuko Miyake; Taku Yamamura; Shoji Tajima; Tohru Funahashi; Yuji Matsuzawa; Akira Yamamoto

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 163 KB
• Volume: 11
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(1998)11:6<480::aid-humu11>3.0.co;2-w

✦ Synopsis

Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in the low density lipoprotein (LDL)-receptor gene. We found a new mutation in the splice acceptor site of intron 1 of the LDL receptor gene, which is designated as 68-1 G->C according to the nomenclature suggested by , in a Japanese FH homozygote. She was born from consanguineous marriage and has this mutation as a true homozygous form. Her cultured fibroblasts showed no LDL receptor protein synthesis. This mutation caused activation of a cryptic splice acceptor site in the downstream exon 2, leading to frameshift and appearance of premature in-frame stop codon. The mutation was detected by Dde I restriction enzyme. The identical mutation was not found among 24 patients with homozygous and 120 patients with heterozygous FH. The mutation was very rare among the Japanese