Charcot Marie Tooth Type 1A
GTR Test Accession: Help GTR000319603.8
INHERITED DISEASENERVOUS SYSTEMSYNDROMIC DISEASE ... View more
Last updated in GTR: 2024-02-07
Last annual review date for the lab: 2024-02-07 LinkOut
At a Glance
Diagnosis; Mutation Confirmation
Charcot-Marie-Tooth disease, type IA; Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome; Hereditary liability to pressure palsies
Genes (1): Help
PMP22 (17p12)
Molecular Genetics - Deletion/duplication analysis: Multiplex Ligation-dependent Probe Amplification (MLPA); Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
CMT1A is a demyelinating peripheral neuropathy characterized by distal muscle …
An estimated 80% of individuals with clinically confirmed HNPP will …
Establish or confirm diagnosis
Ordering Information
Offered by: Help
Molecular Genetics Laboratory
View lab's website
View lab's test page
Test short name: Help
CMT1A
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Licensed Physician
Test Order Code: Help
CMT1A (PMP22)
Lab contact: Help
Gavin Giles, MSc, Administrator
gavin.giles@lhsc.on.ca
+1-519-685-8500 x36339
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order: Help
Please complete the requisition available on the website and provide refering physician signature
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Custom Deletion/Duplication Testing
Custom Sequence Analysis
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)
Informed consent required: Help
Decline to answer
Test strategy: Help
All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; … View more
View citations (1)
  • Schenkel LC, Kerkhof J, Stuart A, Reilly J, Eng B, Woodside C, Levstik A, Howlett CJ, Rupar AC, Knoll JHM, Ainsworth P, Waye JS, Sadikovic B. Clinical Next-Generation Sequencing Pipeline Outperforms a Combined Approach Using Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification in Targeted Gene Panel Analysis. J Mol Diagn. 2016;18(5):657-667. doi:10.1016/j.jmoldx.2016.04.002. Epub 2016 Jul 02. PMID: 27376475.
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Conditions Help
Total conditions: 3
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 1
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 3
Method Category Help
Test method Help
Instrument
Deletion/duplication analysis
Multiplex Ligation-dependent Probe Amplification (MLPA)
Applied Biosystems 3730 capillary sequencing instrument
Deletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Illumina MiSeq/NextSeq
Sequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Applied Biosystems 3730 capillary sequencing instrument
Illumina MiSeq/NextSeq
Clinical Information
Test purpose: Help
Diagnosis; Mutation Confirmation
Clinical validity: Help
An estimated 80% of individuals with clinically confirmed HNPP will harbour a deletion of the PMP22 gene region. A further 20% will harbour point mutations in the PMP22 coding sequence. 70%-80% of individuals with CMT1A will harbour a duplication of the PMP22 gene region
View citations (4)
  • Bird TD. Charcot-Marie-Tooth Neuropathy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1998 Aug 31 [updated 2015 Mar 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301384.
  • Chrestian N. Hereditary Neuropathy with Liability to Pressure Palsies. 1998 Sep 28 [updated 2020 Aug 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301566.
  • https://www.ncbi.nlm.nih.gov/books/NBK1205
  • https://www.ncbi.nlm.nih.gov/books/NBK1392
Clinical utility: Help
Target population: Help
CMT1A is a demyelinating peripheral neuropathy characterized by distal muscle weakness and atrophy, sensory loss, and slow nerve conduction velocity. It is usually slowly progressive and often associated with pes cavus foot deformity and bilateral foot drop. Affected individuals usually become symptomatic between age five and 25 years.
View citations (1)
  • Bird TD. Charcot-Marie-Tooth Neuropathy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1998 Aug 31 [updated 2015 Mar 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301384.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >1000x mean read depth coverage, with a minimum 200x coverage at a single nucleotide resolution. This assay meets the sensitivity and … View more

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Not provided.
Recommended fields not provided:
Technical Information
Test Procedure: Help
All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; … View more
View citations (1)
  • Schenkel LC, Kerkhof J, Stuart A, Reilly J, Eng B, Woodside C, Levstik A, Howlett CJ, Rupar AC, Knoll JHM, Ainsworth P, Waye JS, Sadikovic B. Clinical Next-Generation Sequencing Pipeline Outperforms a Combined Approach Using Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification in Targeted Gene Panel Analysis. J Mol Diagn. 2016;18(5):657-667. doi:10.1016/j.jmoldx.2016.04.002. Epub 2016 Jul 02. PMID: 27376475.
Test Confirmation: Help
All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request.
Availability: Help
Tests performed
Entire test performed in-house

Test performance comments
Testing provided in a state of the art purpose built Molecular Diagnostics facility.
Analytical Validity: Help
The diagnosis of HNPP is established in an adult with recurrent focal compression neuropathies who has a family history consistent with autosomal dominant inheritance. PMP22 is the only gene known to be associated with HNPP. A contiguous gene deletion of chromosome 17p11.2 that includes PMP22 is present in approximately 80% … View more
View citations (4)
  • Bird TD. Charcot-Marie-Tooth Neuropathy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1998 Aug 31 [updated 2015 Mar 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301384.
  • Chrestian N. Hereditary Neuropathy with Liability to Pressure Palsies. 1998 Sep 28 [updated 2020 Aug 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301566.
  • https://www.ncbi.nlm.nih.gov/books/NBK1205
  • https://www.ncbi.nlm.nih.gov/books/NBK1392
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
No
VUS:
Software used to interpret novel variations Help
SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual

Laboratory's policy on reporting novel variations Help
All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request.
Recommended fields not provided:
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
Additional Information

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