Charcot-Marie-Tooth disease testing

Last updated: Wednesday, 11, March, 2009

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Item Process
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 calls 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 susual 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