Braenne, Ingrid and Kleinecke, Mariana and Reiz, Benedikt and Graf, Elisabeth and Strom, Tim and Wieland, Thomas and Fischer, Marcus and Kessler, Thorsten and Hengstenberg, Christian and Meitinger, Thomas and Erdmann, Jeanette and Schunkert, Heribert (2016) Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. EUROPEAN JOURNAL OF HUMAN GENETICS, 24 (2). pp. 191-197. ISSN 1018-4813, 1476-5438
Full text not available from this repository. (Request a copy)Abstract
Familial hypercholesterolemia (FH) is an oligogenic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDLC) levels. Variants in four genes have been reported to cause the classical autosomal-dominant form of the disease. FH is largely under-diagnosed in European countries. As FH increases the risk for coronary artery disease (CAD) and myocardial infarction (MI), it might be specifically overlooked in the large number of such patients. Here, we systematically examined the frequency of potential FH-causing variants by exome sequencing in 255 German patients with premature MI and a positive family history for CAD. We further performed co-segregation analyses in an average of 5.5 family members per MI patient. In total, we identified 11 potential disease-causing variants that co-segregate within the families, that is, 5% of patients with premature MI and positive CAD family history had FH. Eight variants were previously reported as disease-causing and three are novel (LDLR.c.811G>A p.(V271I)), PCSK9.c.610G>A (p.(D204N)) and STAP1.c.139A>G (p.(T47A))). Co-segregation analyses identified multiple additional family members carrying one of these FH variants and the clinical phenotype of either FH (n=2) or FH and premature CAD (n=15). However, exome sequencing also revealed that some variants in FH genes, which have been reported to cause FH, do not co-segregate with FH. The data reveal that a large proportion of FH patients escape the diagnosis, even when they have premature MI. Hence, systematic molecular-genetic screening for FH in such patients may reveal a substantial number of cases and thereby allow a timely LDLC-lowering in both FH/MI patients as well as their variant-carrying family members.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DENSITY-LIPOPROTEIN RECEPTOR; CORONARY-ARTERY-DISEASE; GENERAL-POPULATION; HEART-DISEASE; GENETIC-VARIANTS; MUTATIONS; LDL; CHOLESTEROL; DIAGNOSIS; NETHERLANDS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Mar 2019 09:20 |
| Last Modified: | 13 Mar 2019 09:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2451 |
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