title: [Evaluation of a newly discovered LDL receptor mutation (exon 10, GAC>AAC, D271N, "FH Graz-1") in familial hypercholesterolemia-- a familystudy].
abstract: Heterozygous familial hypercholesterolemia (FH, prevalence 1:500) is a major cause of early atherosclerotic disease. Little is known about possible co-factors influencing individual patient's risk. We investigated this question in a large family carrying a new LDL-receptor-mutation. Genetic analysis of all exons of the LDL-receptor gene in the index case using polymerase chain reaction (PCR) and Denaturing Gradient Gel Electrophoresis (DGGE) revealed a previously unknown mutation in exon 10 (GAC > ACC, D471N, "FH Graz-1"). Investigation of 21 family members (15 females, 6 males), aged 17 to 86 years, revealed 9 female and 4 male carriers of the mutation. 7 female carriers aged 17 to 58 years show no clinical signs of macrovascular disease. An 86-year old female patient, who was asymptomatic until 85, recently suffered a transient cerebral ischemic attack. All these females were normotensive. The only hypertensive 76-year old patient (ex-smoker with a history of 15 pack years) suffers from angina pectoris. 2 male carriers of the mutation (32 and 38 years old) are asymptomatic. A 65-year old patient suffers from cardiovascular disease. A 49-year old patient had a coronary artery bypass graft after a myocardial infarction at the age of 37. Additionally he has a history of bilateral thrombendarterectomy of the carotid arteries and suffers from bilateral peripheral artery disease. This patient also carries the apoE-genotype 4/3, which might be responsible for his poor response to stain therapy, and needs extracorporal lipid elimination (LDL-C > 200 mg/dl under drug therapy). Both of his daughters are homozygous for the apoE-allele 3 and and responded well to stain therapy. Genetic analysis in patients with FH assures diagnosis, but is not sufficient to determine the individual patient's risk. A precise clinical examination remains the gold standard for individual risk evaluation.
authors.affiliation: Ambulanz für Diabetes und Stoffwechsel, Medizinischen Universitätsklinik Graz.
authors.forename: A
authors.initials: A
authors.lastname: de Campo
authors.forename: H
authors.initials: H
authors.lastname: Toplak
authors.forename: T C
authors.initials: TC
authors.lastname: Wascher
authors.forename: K
authors.initials: K
authors.lastname: Schallmoser
authors.forename: A
authors.initials: A
authors.lastname: Friehs
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: G M
authors.initials: GM
authors.lastname: Kostner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001794:Blood Pressure; D005091:Exons; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL