Question 206

Question:

A 20-year-old man comes to the physician’s office for a scheduled health maintenance
examination. His father died of a myocardial infarction at age 55 years. Physical examination shows a tendon xanthoma on the elbow. His serum total cholesterol concentration is 360 mg/dL. A mutation is most likely to be found in which of the following genes?

Correct Answer: D.  LDL receptor

This patient most likely has familial hypercholesterolemia, an autosomal dominant disorder associated with a deficiency in LDL receptors (choice D). The rise in his cholesterol concentration is most likely due to a decrease in LDL receptor-mediated endocytosis of cholesterol-rich LDL. Tendon xanthomas are a typical feature of LDL receptor deficiency. In contrast, yellow papular skin lesions, or eruptive xanthomas, are a typical feature of a mutation in the VLDL receptor gene (choice E) and apoC2 (choice B).
A mutation in apoA2 (choice A) would interfere with HDL cholesterol and would not lead to skin manifestations.
A mutation in apoE4 (choice C) would cause an increase in both triglycerides and cholesterol and there may be yellow deposits in the skin creases on the palms on physical exam.