While genetic testing laboratories can be trusted to find variants in a gene’s coding sequence, not all laboratories do comparable interpretations. Working with a provider who has confidence in a given laboratory should be the first step in getting ready to do genetic testing. A provider should collect information about the following questions to help provide interpretation of the results:
- Is there already a genetic diagnosis in the family? If so, other family members only need testing for the same variant.
- What do the nerve conduction studies show? Demyelinating conductions should have PMP22 dup/del testing first, then other genes that cause demyelinating CMT. Axonal conductions may need a larger panel, but the chance of finding the answer for people with axonal CMT is lower than demyelinating CMT.
- What is the pattern of inheritance in the family? Are multiple family members affected? Are they in the same generation (siblings) or in different generations (parent, child)? Are there any dads who passed the condition on to their sons?
Conductions and inheritance are important in interpreting lab results. Often, variants of uncertain significance (VUS) are found in genetic testing. If there is a VUS in an axonal gene, but a person has demyelinating conductions, that is likely not the cause of the CMT. Some genes are known to be either dominant (only one gene needs to have a disease causing variant to be affected) or recessive (both copies of the gene need to have disease causing variants). The inheritance pattern can be helpful for interpreting variants.
Genetic testing is constantly evolving. Insurance coverage can also be challenging to understand. Many labs now will run a benefits investigation and let you know your out-of-pocket costs before doing the testing. The best tip is to be your own advocate. Genetic counselors, who can help determine the best test and the best lab, can be found at www.nsgc.org.
*Carly is a senior genetic counselor in the Neuromuscular Division at Stanford Health Care and has worked with CMT for over a decade. A major function of her job is determining appropriate genetic testing and the laboratory to which the testing will be sent.