Hereditary Motor and Sensory Neuropathy: PMP22 Duplication / Deletion Analysis

Test Identifier Information

Duplication and deletion of the PMP22 gene is detected by Multiplex Ligation Dependant Probe Amplification (MLPA) using the MRC-Holland SALSA MLPA kit P033 CMT1.

The hereditary motor and sensory neuropathies (HMSN) are a heterogeneous group of peripheral neuropathies with a combined incidence of 30:100,000. Charcot-Marie-Tooth Type 1, CMT1 is the most common clinical form of HMSN with an incidence of 15:100,000. It is usually inherited as an autosomal dominant condition and is characterised by slowly progressive distal limb muscle weakness and atrophy affecting the peroneal muscles. Onset is typically in the first or second decade of life although considerable variation in clinical presentation is observed. Life expectancy is not changed.
The most common subtype of CMT1 is called CMT1A, caused by duplication of the PMP22 gene on chromosome 17p11.2. In approximately one third of cases, duplication occurs de novo. CMT1A comprises approximately 70% of CMT1.
The genetically related condition “Hereditary Neuropathy with liability to Pressure Palsies” (HNPP) is an inherited recurrent focal neuropathy, characterised by painless nerve palsies following mild pressure or trauma. Peripheral nerve biopsy reveals sausage-shaped thickenings on the myelin sheath termed tomaculae. Therefore this condition is also known as Tomaculous Neuropathy. HNPP varies in severity and age of onset, and often remains undiagnosed. In all reported cases, it occurs as a result of deletion of the PMP22 gene.
 

Specimen Collection

MLPA based assays are sensitive to the buffer used in DNA extraction processes. Due to this, our preference is to recieve whole blood (EDTA) which will then be extracted at Canterbury Health Laboratories. Processing of DNA extracted at other centers may result in a request for a new sample if the analysis is compromised.

CHLabs Laboratory

A negative result does not exclude a diagnosis of CMT1. Other genes causing CMT1 include MPZ (CMT1B, 10%), LITAF (CMT1C, 2%), and point mutations in PMP22 (CMT1E, <5%).

1. This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
2. Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms / microlitre.

3. If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).