Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.
Article Details
- CitationCopy to clipboard
Nauck MS, Koster W, Dorfer K, Eckes J, Scharnagl H, Gierens H, Nissen H, Nauck MA, Wieland H, Marz W
Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.
Hum Mutat. 2001 Aug;18(2):165-6.
- PubMed ID
- 11462246 [ View in PubMed]
- Abstract
In order to identify mutations in the low density lipoprotein receptor (LDLR) gene in primary hypercholesterolemia, we screened 100 unrelated German individuals with elevated plasma LDL-C (LDL-C > 4,7 mmol/l) for mutations in the 18 exons and their flanking intronic sequences including the promoter region of the LDL-R gene using a combination of polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct sequencing. In addition we tested all patients for the presence of mutations in codons 3456 - 3553 of the gene encoding apolipoprotein B-100. In 56 individuals we detected 37 different mutations affecting the LDL-R gene, 16 of which, designated C122R, C127Y, C163W, F179L, R236W, E296X, R553C, V618D, T721I, V785D, G1358+2A, 257delTCTGGAGGT, 657delC, 676insACGGTATGGACTGCAdelGACG, C1205delTCT, 2420delTCCTTCT, have not yet been reported. One proband was a compound heterozygote showing two separate sequence variations (E207X and T705I). Seven patients were heterozygous for the mutation R3500Q within the apoB-100 gene. These results demonstrate that there is a broad spectrum of mutations in the LDL-R gene and that the R3500Q mutation is a frequent cause of hypercholesterolemia in the German population.