What are the classes of genetic mutations in familial hypercholesterolemia (FH)?

Updated: Oct 04, 2021
  • Author: Mose July, MD, CCD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

Five classes of mutations have been defined as follows:

  • Class 1 includes null alleles that result in complete absence of the LDL receptor.

  • Class 2 includes defective transport alleles, which disrupt normal folding of the receptor and cause either failure in transport to the cell surface or successful transport of truncated, mutated receptors.

    • Class 2a mutations completely block the transport of the receptor from the endoplasmic reticulum to the Golgi apparatus.

    • Class 2b mutations result in a partial blockade of transport of the receptor from the endoplasmic reticulum to the Golgi apparatus.

  • Class 3 includes defective binding alleles that affect binding of LDL and, in some cases, binding of VLDL as well.

  • Class 4 includes defective internalization alleles that affect the concentration of normal receptors in clathrin-coated pits for internalization by the hepatocyte.

  • Class 5 includes defective recycling alleles that prevent dissociation of the receptor and the ligand and thereby interrupt recycling of the receptor.


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