The Figure illustrates the known mutations that can give rise to FH.
- The first one is the LDL receptor defect. Multiple defects have been
described in the LDL receptor gene found on chromosome number 19, this
is the most common genetic cause for FH.
- A second defect concerns ApoB, the ligand for the LDL receptor, which also gives rise to the phenotype of FH.
- A third defect is a gain-of-function mutation in the PCSK9 gene; PCSK9
is a serine protease that degrades or destroys the LDL receptor; people with this
gain-of-function mutation experience increased degradation of their LDL
receptors, resulting in an elevation of circulating LDL-C.
- Finally, homozygotes for the autosomal recessive defect in the LDL RAP1
gene have LDL particles that are able to bind to the LDL receptors but
are unable to internalize into the coated pits in the liver.
These are the genetic variants that are known to result in FH, although
there are certainly others that are yet to be identified.
