Key result
Targeted genetic testing identifies causal mutations, primarily LDLR, in ~60% of North American FH patients.
Why the study?
Familial hypercholesterolemia is commonly caused by mutations in LDLR, APOB, or PCSK9 genes, but the prevalence of these mutations and clinical differences in mutation-positive versus mutation-negative subjects in North America are not fully characterized.
What is the prevalence of pathogenic mutations in known culprit genes in patients meeting Simon Broome criteria for familial hypercholesterolemia?
Cohort (n=200)
Yes
What is the prevalence of pathogenic mutations in known culprit genes in patients meeting Simon Broome criteria for familial hypercholesterolemia?
A significant proportion (40%) of North American patients meeting clinical criteria for familial hypercholesterolemia lack mutations in known culprit genes, highlighting the need to identify other genetic and environmental factors.
No takes yet. Share an insight, caveat, or question.
May warrant broader genetic panels in clinically diagnosed FH; leaves open discovery of novel variants and modifiers.
Garg et al. (2019) conducted a cohort in Familial hypercholesterolemia (n=200). Pathogenic mutations in LDLR, APOB, and PCSK9 vs. No mutations in known culprit genes was evaluated on Prevalence of pathogenic mutations in LDLR, APOB, and PCSK9. In a North American cohort of patients with familial hypercholesterolemia, 60% had disease-causing mutations (primarily LDLR), while 40% lacked mutations in known culprit genes.
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