Familial hypercholesterolemia (FH) is an oligogenic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDLC) levels.
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, Ingrid Brænne et al. 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. Our data reveal that a large proportion of FH patients indeed 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.
In conclusion, our work demonstrates that exome sequencing can be used for FH-variant screening.
As the sequencing costs have decreased dramatically, exome sequencing might become the method of choice for molecular genetic screening of, for instance, FH.