title: Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.
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.
authors.affiliation: Department of Clinical Chemistry, University Hospital, Freiburg, Germany.
authors.forename: M S
authors.initials: MS
authors.lastname: Nauck
authors.forename: W
authors.initials: W
authors.lastname: Köster
authors.forename: K
authors.initials: K
authors.lastname: Dörfer
authors.forename: J
authors.initials: J
authors.lastname: Eckes
authors.forename: H
authors.initials: H
authors.lastname: Scharnagl
authors.forename: H
authors.initials: H
authors.lastname: Gierens
authors.forename: H
authors.initials: H
authors.lastname: Nissen
authors.forename: M A
authors.initials: MA
authors.lastname: Nauck
authors.forename: H
authors.initials: H
authors.lastname: Wieland
authors.forename: W
authors.initials: W
authors.lastname: März
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics*; D002648:Child; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D018899:CpG Islands / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005858:Germany; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D003062:Codon; D011973:Receptors, LDL