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Genetic Testing for Autosomal Dominant Hypercholesterolemia

Familial Defective ApoB-100

Slide 9

December 2008

A second genetic disease that falls under the ADH umbrella is Familial Defective ApoB-100, or FDB. It’s responsible for about 15% of ADH. FDB is caused by mutations in the APOB gene, which encodes apolipo-protein B-100. This is the major protein component of LDL.  FDB-causing mutations in APOB result in defective binding of LDL to LDLR, leading to elevated plasma levels of LDL.

The most common APOB mutation is R3500Q, and it occurs at a frequency of about 1 in 500 to 1 in 700 in the Caucasian population. A rarer mutation that has been shown to occur repeatedly in individuals with FDB is the R3500W mutation. This has been shown mainly in individuals of Scottish and Asian ancestry and it accounts for about 2% of FDB. While the frequency of APOB mutations is relatively high, it is important to note that the penetrance of APOB mutations are not as high as the penetrance of LDLR mutations, thus explaining the lower phenotypic mutation of FDB compared to the frequency of the APOB mutations.  In addition, the severity of FDB is generally not as high as FH, and only  about 40% of male and 20% of female APOB mutation carriers are predicted to develop CAD.

Familial Defective ApoB-100


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