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Forschungsdatenbank PMU-SQQUID

[Evaluation of a newly discovered LDL receptor mutation (exon 10, GAC>AAC, D271N, "FH Graz-1") in familial hypercholesterolemia-- a familystudy].
de Campo, A; Toplak, H; Wascher, TC; Schallmoser, K; Friehs, A; Schmidt, H; Kostner, GM;
Acta Med Austriaca. 1999; 26(1): 20-25.
Originalarbeiten (Zeitschrift)


Schallmoser Katharina


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.

Useful keywords (using NLM MeSH Indexing)




Aged, 80 and over

Amino Acid Substitution

Blood Pressure




Hyperlipoproteinemia Type II/genetics*

Hyperlipoproteinemia Type II/physiopathology


Ischemic Attack, Transient/genetics


Middle Aged


Point Mutation*

Polymerase Chain Reaction

Receptors, LDL/genetics*

Find related publications in this database (Keywords)

familial hypercholesterolemia
LDL-receptor mutation
genetic diagnosis
exon 10
lipid profile
atherosclerosis risk