A diagnosis of HoFH was based on at least one of the following criteria: documented functional mutation/mutations in both LDLR alleles, the presence of homozygous or compound heterozygous mutations in apo B or PCSK9, double heterozygotes or patients with homozygous LDLRAP1 mutations or an untreated total cholesterol level >500 mg/dl and triglycerides <300 mg/dl, and either both parents with documented total cholesterol >250 mg/dl or cutaneous or tendinous xanthoma before 10 years of age. The gene discussed is PCSK9; the disease is homozygous familial hypercholesterolemia.