Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:Q9ULZ2 (
STAP1
)
11
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. 2603 59
