Familial Hypercholesterolemia

Gene: LDLR

Protein: low density lipoprotein receptor

Gene: PCSK9

Protein: proprotein convertase, subtilisin/kexin-type 9

Gene: APOB

Protein: apolipoprotein B

Clinical Characteristics

  • Hypercholesterolemia, usually present from birth
    • Heterozygous:
      • Total cholesterol of 250-450 mg/dl
      • LDL-cholesterol of 200-400 mg/dl
    • Homozygous:
      • Total cholesterol greater than 500 mg/dl
      • LDL-cholesterol greater than 450 mg/dl
  • Corneal arcus
  • Xanthomas, around eyelids, on tendons and between fingers
  • Increased risk of coronary heart disease (CHD) at an early age
    • Heterozygous: CHD in 40’s or 50’s if untreated
    • Homozygous: severe CHD often fatal before age 20 if untreated

Inheritance pattern: Autosomal co-dominant

What Can Be Learned From This Test

Testing is performed by a tiered approach.

Tier 1 includes sequencing exons 1-4, 9-11, and 17 of LDLR, exon 7 of PCSK9, and the portion of exon 26 in APOB containing common pathogenic variants.

Tier 2 includes sequencing the remaining exons of LDLR and PCSK9, an additional fragment of exon 26 of APOB containing other published pathogenic variants, and deletion/ duplication testing of select exons of LDLR and PCSK9.

The sequencing tests will detect point mutations, small deletions, and small insertions. The deletion/ duplication tests may not detect a partial copy number variant, but will detect a whole gene deletion or duplication. Large deletions and duplications in LDLR have been reported.

Sample Requirements

Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).

Turnaround time: 10-14 business days per tier

CPT Codes and Cost

Tier 1

  • Codes: 81401, 81406, 81479 
  • Cost: $370

Tier 2

  • Codes: 81401, 81405, 81406, 81479 x3 
  • Cost: $1,050

Both Tiers

  • Codes: 81401, 81405, 81406 x2, 81479 
  • Cost: $1,420

Known Variant Testing

  • Code: 81479 
  • Cost: $225

Additional Information