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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)

PMU-Autor/inn/en

Schallmoser Katharina

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.


Useful keywords (using NLM MeSH Indexing)

Adolescent

Adult

Aged

Aged, 80 and over

Amino Acid Substitution

Blood Pressure

Exons

Female

Humans

Hyperlipoproteinemia Type II/genetics*

Hyperlipoproteinemia Type II/physiopathology

Hypertension/genetics

Ischemic Attack, Transient/genetics

Male

Middle Aged

Pedigree

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