Open AccessA Single Point Mutation in the Splice Donor Site of the Low‐Density‐Lipoprotein‐Receptor Gene Produces Intron Read‐Through, Exon‐Skipped and Cryptic‐Site‐Utilized Transcripts
Author(s) -
Maruyama Takao,
Miyake Yasuko,
Tajima Shoji,
Funahashi Tohru,
Matsuzawa Yuji,
Yamamoto Akira
Publication year - 1995
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1995.700zz.x
Subject(s) - intron , exon , splice site mutation , point mutation , rna splicing , splice , genetics , biology , ldl receptor , gene , mutation , microbiology and biotechnology , alternative splicing , lipoprotein , rna , endocrinology , cholesterol
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.