Charcot-Marie-Tooth disease testing

Specimen:

5-10 ml blood in EDTA tube.

Method:

1. MLPA (multiplex ligase-dependant probe amplification) to detect the submicroscope tandem duplication of a 1.5Mb region associated with CMT and the deletion of the same region associated with HNPP. THis region encompasses the gene peripheral myelin protein 22 (PMP22) located at chromosome region 17p11.2-p.12.

2. FISH on interphase cells to detect the duplication associated with CMT 1A. FISH on metaphases to detect the deletion associated with HNPP.

Application:

Used in conjunction with neurophysiological studies to diagnose CMT type 1A and HNPP (also called tomaculous neuropathy).

Interpretation:

Current MPLA method detects the 1.5Mb duplication which is responsible for most (98%) of CMT type 1A cases. It also detects the deletion in this region which is the most usual cause of HNPP. FISH is a sensitive method to detect deletions but is less sensitive in detecting duplications.

The identification of a duplication of the PMP22 gene is diagnostic of Type IA Charcot-Marie-Tooth disease.

A deletion within the gene is diagnostic of tomaculous neuropathy.

The identification of a mutation does not predict the age of onset or severity.

Molecular genetic studies may be indicated in other family members.

The absence of a mutation does not exclude the diagnosis and family studies may clarify a person’s carrier status.

Reference:

Slater H. Human Mutation 2004; 24:164-171