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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
Author(s) -
Maruyama Takao,
Miyake Yasuko,
Yamamura Taku,
Tajima Shoji,
Funahashi Tohru,
Matsuzawa Yuji,
Yamamoto Akira
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)11:6<480::aid-humu11>3.0.co;2-w
Subject(s) - frameshift mutation , exon , biology , splice site mutation , point mutation , genetics , mutation , intron , familial hypercholesterolemia , ldl receptor , microbiology and biotechnology , gene , stop codon , lipoprotein , alternative splicing , endocrinology , cholesterol
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 Beaudet and Tsui (1993), 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 population. Hum Mutat 11:480–481, 1998. © 1998 Wiley‐Liss, Inc.