Charcot-Marie-Tooth Disease Type 1A: PMP22 Deletion/Duplication MLPA

Clinical Information

Charcot-Marie-Tooth (CMT) disease is the most common form of inherited peripheral neuropathy, and these conditions have a prevalence of approximately 1 in 3000 individuals. Clinical symptoms include distal muscle weakness with atrophy, loss of deep tendon reflexes, high-arched feet, and loss of sensation. These conditions tend to be progressive, and while most families demonstrate autosomal dominant inheritance, autosomal recessive and X-linked inheritance also occurs. Symptoms and age of onset are variable, but early signs of the disorder include clumsiness, balance problems, and difficulty using the hands to grasp. Hearing loss occurs in some affected individuals, and eventually, some patients require the assistance of a wheelchair. Lifespan and intelligence are not typically affected.

Charcot-Marie-Tooth disease is comprised of several types and subtypes. CMT1 is responsible for almost half of all cases of CMT, with CMT2 and CMTX making up an additional 10-15% each. Within the CMT1 type, about 70-80% of cases are due to changes in the PMP22 most often associated with a duplication involving chromosome 17p12. Reciprocal deletions of this region are associated with hereditary neuropathy with liability to pressure palsies, HNPP.

Technical Information

• This test is performed using Multiplex Ligation-dependent Probe Amplification (MLPA).
• MLPA analysis is performed to determine if deletions or duplications involving the peripheral myelin protein 22 (PMP22) gene are present. MLPA is a molecular technique that allows the determination of dosage for specific sequences of interest (Schouten et al. (2002) Nucleic Acids Research 30, e57).
• For this test, probes for the CMT/HNPP region including PMP22, as well as probes in the MPZ and GJB1 genes and a variety of control probes, are analyzed and quantified.

Specimen Requirements

• The preferred sample type is 3-4 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Blood and saliva kits are available by request.
• Send approximately 5µg of extracted DNA at a requested concentration of 90-130 ng/µl.
• Saliva samples must be submitted in an approved saliva kit.

Transport Instructions

• The blood specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.
• Extracted DNA should be sent at room temperature via overnight delivery.
• Saliva is stable at room temperature and can be delivered via overnight or ground shipping.