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HelpTest Code LAB3393 PMP22 Deletion/Duplication
Additional Codes
PMP22DD
Clinical System Name
PMP22 Deletion/Duplication
Synonyms
Charcot-Marie-Tooth Hereditary Neuropathy
CMT
Sample Requirements
Preferred Specimen: Whole Blood
Container(s): Lavender Top/EDTA
Preferred Vol: 5.0 mL
Minimum Vol: 2.0 mL (1.0 mL is acceptable for infants)
Alternative Specimen: DNA
Container(s): Sterile plastic tube
Preferred Vol: 5 µg at a concentration of ≥50 ng/µL AND a volume of ≥100 µL
Alternative Specimen: Buccal Swab
Processing Instructions
Reject due to:
Spin: N
Aliquot: N
Temp: 2 - 8 C
Storage location: Affix a large Epic label to the sample(s) and place in the CPA1 refrigerator, Send Outs rack.
Off-site collection: Send whole blood refrigerated.
Stability
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood | Room temp | 3 d |
| Whole Blood | Refrigerated | 7 d |
| Whole Blood | Frozen | Unacceptable |
| Extracted DNA | Room temp | 3-4 d |
| Extracted DNA | Refrigerated | 1 y |
Availability
| STAT | TAT |
|---|---|
| N | 2 w |
Performing Laboratory
GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
Phone Number: (301) 519-2100
Department
Department: Send Outs/Genetic
Phone: (206) 987-2563
Methodology
Method: Exon-level arrayCGH
Targeted array CGH analysis with exon-level resolution is performed to evaluate for a deletion or duplication of one or more exons of the gene. The presence of any potentially disease-associated copy number alteration(s) is confirmed by quantitative PCR or another appropriate method. Sequencing and deletion/duplication analysis of the remaining genes on the Hereditary Neuropathy Panel is available as a separate test if this test negative.
Reference Range
Interpretive report is provided.
Send Out Instructions
| Reference Test Name: |
PMP22 Del/Dup |
| Reference Lab Test Code: | 742 |
| Instructions: |
GeneDx accepts Saturday delivery. Whole blood specimens may be stored refrigerated for up to 7 days prior to shipping. Ship overnight via FedEx M - F, ambient temperature. |
Description
This test performs deletion/duplication analysis of PMP22. Variants in PMP22 are associated with Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) and Charcot-Marie-Tooth 1A (CMT1A).
Clinical Utility
Hereditary neuropathy with liability to pressure palsy (HNPP): is characterized by recurrent episodes of sensory and motor neuropathy in a single nerve. While any nerve in the peripheral nervous system can be affected, the ulnar, peroneal, median, brachial plexus and radial nerves are most commonly affected. Almost all affected individuals show prolongation of distal nerve conduction latencies. Other features include: reduced or absent tendon reflexes, pes cavus, episodic foot drop, atrophy and weakness of the hands, carpal tunnel syndrome, and pain, while less common features include: motor brachial paralysis, proximal muscle atrophy, respiratory insufficiency, white matter lesions on brain MRI, hypoglossal nerve paralysis of the tongue, and scapuloperoneal syndrome. An episode can last from minutes to months. Individuals typically present in the 2nd or 3rd decade, although the age of onset can range from neonatal period into the 7th decade.
Charcot-Marie-Tooth type 1A (CMT1A):is a progressive disorder characterized by slow nerve conduction velocity (less than 38m/s), distal muscle weakness and atrophy, depressed deep tendon reflexes, sensory loss, pes cavus, hammertoes, and bilateral foot drop. Hearing loss and hip dysplasia may also be present. Approximately 85% of individuals with CMT1A present with initial symptoms before age 20.
HNPP is most commonly caused by a 1.5Mb deletion on the short arm of chromosome 17, which includes the PMP22 gene. While approximately 80% of individuals with HNPP have this recurrent deletion, the remaining 20% have point variants in the PMP22 gene. The reciprocal duplication of PMP22 is the most common cause of Charcot-Marie-Tooth disease. Approximately 70% of CMT1 is caused by the recurrent PMP22 duplication. Other causes of demyelinating CMT include: point variants in PMP22, and pathogenic variants in MPZ, LITAF, EGR2, and NEFL.
Exon-level arrayCGH will detect partial and whole gene deletions and duplications of the PMP22 gene. Approximately 80% of individuals with a HNPP will have a deletion of PMP22, while approximately 70% of individuals with CMT1 will have a duplication of the PMP22 gene.
A genetic diagnosis may have implications for treatment, management, recurrence risk, and family member testing.