Genetic Testing for Autosomal Dominant Hypercholesterolemia

ADH-Genetic Testing Methodology

December 2008

Given all the information provided here thus far, it is apparent that genetic testing for ADH is important in many cases. Now I would like to take the opportunity to describe the genetic testing methodology that we employ at Mayo as well as take you through our ADH genetic test reflex algorithm.

The first part of our test involves targeted mutation analysis of the two common APOB mutations. The second part of our test involves sequencing of all 18 exons and the promoter of LDLR.  The sequencing assay will allow us to detect point mutations and small insertion/deletion-type mutations. The final aspect of our ADH genetic testing involves a gene dosage method to identify the LDLR gene rearrangements or exonic deletions and duplications that were discussed earlier. As mentioned, these types of mutations account for about 10-15% of all LDLR mutations. It is important to note that we require a method alternative to sequencing in order to detect this type of mutation.

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ADH-Genetic Testing Methodology

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Jump to section:

• Introduction
• Autosomal Dominant Hypercholesterolemia
• Autosomal Dominant Hypercholesterolemia
• Autosomal Dominant Hypercholesterolemia
• Familial Hypercholesterolemia
• FH-Primary Defect in LDLR
• LDLR Gene
• LDLR Gene
• Familial Defective ApoB-100
• How is ADH Diagnosed?
• Impact of Failure to Diagnose
• Why is Genetic Testing for ADH Useful?
• Statin Treatment-How Early?
• ADH-Genetic Testing Methodology
• Familial/Autosomal Dominant Hypercholesterolemia Diagnostic Algorithm
• APOB-Targeted Genotyping Performed First
• APOB Mutation-Positive
• APOB Mutation-Negative
• LDLR Sequence Mutation-Positive
• LDLR Sequence Mutation-Negative
• LDLR Large Del/Dup Mutation-Positive
• LDLR Large Del/Dup Mutation-Negative
• Summary
• Conclusion
• Questions?