Mutations in low-density lipoprotein receptor gene as a cause of hypercholesterolemia in Taiwan.
Familial hypercholesterolemia (FH) is inherited as an autosomal dominant trait that has been associated with more than 920 different mutations in the low-density lipoprotein receptor (LDLR) gene. To characterize LDLR gene mutations in the Chinese of Han descent with FH, we isolated genomic DNA from peripheral blood samples of 20 affected subjects and 50 healthy subjects with no family history of hypercholesterolemia. We used polymerase chain reaction and long polymerase chain reaction to amplify the 18 coding exons and the minimal promoter of the LDLR gene, and subjected amplicons to direct sequence analysis. We identified 6 mutations in LDLR gene, including heterozygous missense mutations I420T (ATC-->ACC), C660W (TGC-->TGG), H562Y (CAC-->TAC), and A606T (GCC-->ACC), and a heterozygous and a homozygous mutation in codon P664L (CCG-->CTG) as well as a homozygous large deletion of exons 6 to 8. The FH homozygotes manifested generalized xanthomatosis. One of the mutations we identified (C660W) was novel. In conclusion, we identified 5 missense mutations and 1 large deletion in LDLR gene, including 1 novel mutation in Han Chinese with FH in Taiwan.
Chiu
Chih-Yang
CY
Section of Biochemistry, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC 112.
Wu
Yi-Chi
YC
Jenq
Shwu-Fen
SF
Jap
Tjin-Shing
TS
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
D011973:Receptors, LDL