Test Catalog

Test Id : NPPAN

Peripheral Neuropathy Genetic Panels, Next-Generation Sequencing (NGS), Blood

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of inherited peripheral neuropathies associated with known causal genes

 

Serving as a second-tier test for patients in whom previous targeted gene variant analyses for specific inherited peripheral neuropathy-related genes were negative

 

Identifying variants within genes known to be associated with inherited peripheral neuropathy, allowing for predictive testing of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This ordered service includes the option for one of several peripheral neuropathy related panel tests to be performed. The specific peripheral neuropathy panel requested must be provided in order to perform this test. Testing options include the following:

 

-Hereditary Motor Neuropathy Panel (23 genes)

-Hereditary Sensory Neuropathy Panel (18 genes)

-Metabolic or Syndromic Neuropathies (74 genes)

-Motor and Sensory Neuropathy Panel (82 genes)

-Peripheral Neuropathy Expanded Panel (193 genes)

-SEPT9 Gene, Full Gene Analysis (1 gene)

-Spastic Paraplegia Neuropathy Panel (41 genes)

-Custom Gene Panel (https://orders.mayocliniclabs.com/en/tools/gene_panels/)

-Custom Gene Ordering tutorial: https://vimeo.com/299737728/23d56922f1

See Frequently Asked Questions: Custom Gene Ordering Tool in Special Instructions.

 

See Targeted Genes and Methodology Details for Peripheral Neuropathy Gene Panels in Special Instructions for details regarding the targeted genes for each test.

 

*Related testing to neuromuscular conditions is available. See NMPAN / Neuromuscular Genetic Panels by Next-Generation Sequencing (NGS) for more information about neuromuscular testing.

Highlights

This test may aid in the diagnosis of inherited peripheral neuropathy

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
_G103 Peripheral Neuropathy Expanded Panel No, (Bill Only) No
_G104 Motor and Sensory Neuropathy Panel No, (Bill Only) No
_G105 Hereditary Sensory Neuropathy Panel No, (Bill Only) No
_G106 Hereditary Motor Neuropathy Panel No, (Bill Only) No
_G107 Spastic Paraplegia Neuropathy Panel No, (Bill Only) No
_G108 Metabolic or Syndromic Neuropathies No, (Bill Only) No
_G132 SEPT9 Gene, Full Gene Analysis No, (Bill Only) No
G145 Hereditary Custom Gene Panel Tier 1 No, (Bill Only) No
G146 Hereditary Custom Gene Panel Tier 2 No, (Bill Only) No
G151 Custom Gene Panel(CPT 81448) Tier 2 No, (Bill Only) No
G152 Custom Gene Panel(CPT 81448) Tier 3 No, (Bill Only) No
G153 Custom Gene Panel(CPT 81448) Tier 4 No, (Bill Only) No
G154 Custom Gene Panel(CPT 81448) Tier 5 No, (Bill Only) No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes the option for either one of several predefined panel tests or the option to create a custom gene panel. Pricing for the Custom Gene Panel will be based on the number of genes selected (1, 2-4, 5-14, 15-49, 50-100, and 101-500). See Custom Gene Panel Ordering in Special Instructions.

 

See Hereditary Peripheral Neuropathy Diagnostic Algorithm in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS)/Polymerase Chain Reaction (PCR)/qPCR, Sanger Sequencing/and/or Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Peripheral Neuropathy Gene Panels

Aliases
Lists additional common names for a test, as an aid in searching

Charcot-Marie-Tooth disease

Charcot Marie Tooth

CMT

Dejerine-Sottas disease

dHMN

Distal hereditary motor neuropathy

Familial neuropathy

Hereditary motor and sensory neuropathy

Hereditary sensory and autonomic neuropathy

Hereditary spastic paraplegia

HMSN

HNPP

HSAN

HSN

HSP

Inherited neuropathy

Inherited peripheral neuropathy

Metabolic neuropathy

MPZ

PMP22

Spastic paraplegia

Syndromic neuropathy

Familial Brachial Plexus Neuritis

Hereditary Neuralgic Amyotrophy

Heredofamilial Neuritis with Brachial Plexus Predilection

HNA

SEPT9

SEPTS

SEPTZ

Custom Gene Ordering

Custom Gene Panel

Custom NGS Panel

Custom ordering

Custom Panels

Custom Sequencing Panels

Custom sequencing test

Customizable Epilepsy Panels

Customizable Hereditary Panels

Customizable Panels

A la carte

Next Gen Sequencing

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes the option for either one of several predefined panel tests or the option to create a custom gene panel. Pricing for the Custom Gene Panel will be based on the number of genes selected (1, 2-4, 5-14, 15-49, 50-100, and 101-500). See Custom Gene Panel Ordering in Special Instructions.

 

See Hereditary Peripheral Neuropathy Diagnostic Algorithm in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

The recommended first-tier test to screen for hereditary motor and sensory neuropathy is PMPDD / PMP22 Gene, Large Deletion and Duplication Analysis, Varies, which assesses for large deletions and duplications of the PMP22 gene.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
MG112 Specify Sub-Panel from Catalog Hereditary Motor Neuropathy Panel
Hereditary Sensory Neuropathy Panel
Metabolic or Syndromic Neuropathies
Motor and Sensory Neuropathy Panel
Peripheral Neuropathy Expanded Panel
SEPT9 Gene, Full Gene Analysis
Spastic Paraplegia Neuropathy Panel
Custom Gene Panel
MG121 Gene List ID or NA

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Neurology Patient Information in Special Instructions.

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
Frozen
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of inherited peripheral neuropathies associated with known causal genes

 

Serving as a second-tier test for patients in whom previous targeted gene variant analyses for specific inherited peripheral neuropathy-related genes were negative

 

Identifying variants within genes known to be associated with inherited peripheral neuropathy, allowing for predictive testing of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This ordered service includes the option for one of several peripheral neuropathy related panel tests to be performed. The specific peripheral neuropathy panel requested must be provided in order to perform this test. Testing options include the following:

 

-Hereditary Motor Neuropathy Panel (23 genes)

-Hereditary Sensory Neuropathy Panel (18 genes)

-Metabolic or Syndromic Neuropathies (74 genes)

-Motor and Sensory Neuropathy Panel (82 genes)

-Peripheral Neuropathy Expanded Panel (193 genes)

-SEPT9 Gene, Full Gene Analysis (1 gene)

-Spastic Paraplegia Neuropathy Panel (41 genes)

-Custom Gene Panel (https://orders.mayocliniclabs.com/en/tools/gene_panels/)

-Custom Gene Ordering tutorial: https://vimeo.com/299737728/23d56922f1

See Frequently Asked Questions: Custom Gene Ordering Tool in Special Instructions.

 

See Targeted Genes and Methodology Details for Peripheral Neuropathy Gene Panels in Special Instructions for details regarding the targeted genes for each test.

 

*Related testing to neuromuscular conditions is available. See NMPAN / Neuromuscular Genetic Panels by Next-Generation Sequencing (NGS) for more information about neuromuscular testing.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes the option for either one of several predefined panel tests or the option to create a custom gene panel. Pricing for the Custom Gene Panel will be based on the number of genes selected (1, 2-4, 5-14, 15-49, 50-100, and 101-500). See Custom Gene Panel Ordering in Special Instructions.

 

See Hereditary Peripheral Neuropathy Diagnostic Algorithm in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Inherited peripheral neuropathies are a relatively common diverse group of disorders with heterogeneous genetic causes. Due to the considerable overlap in the clinical phenotypes of various neuropathies, it is often difficult to distinguish these specific inherited disorders from sporadic, idiopathic, or acquired forms of neuropathy without genetic testing. Additionally, peripheral neuropathy may be part of an inherited systemic syndromic or metabolic disorder caused by genes in metabolic pathways. Based on the pattern of inheritance and nerve conduction studies, there are 3 major categories of inherited peripheral neuropathies with isolated nerve involvement:

1. Hereditary motor and sensory neuropathy (HMSN), also referred as Charcot Marie Tooth (CMT)

2. Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN), if autonomic dysfunction is absent

3. Distal hereditary motor neuropathy (dHMN)

 

Inherited peripheral neuropathies may also show involvement of the central nervous system (brain or spinal cord), as in hereditary spastic paraplegia (HSP) with neuropathy (complicated form, also referred to as HMSN type 5) or be part of a systemic syndromic or metabolic disorder.

 

Hereditary Motor and Sensory Neuropathy:

HMSN, or CMT disease, is a major category of inherited peripheral neuropathies and is the most commonly inherited neuromuscular disorder. It is characterized by motor or sensory peripheral nerve involvement. The clinical phenotype is variable and includes wasting and weakness of the distal limb muscles, skeletal deformities, and hearing loss. HMSN/CMT is classified into 5 groups:

1. HMSN 1, which is a dominantly inherited demyelinating form

2. HMSN 2, a dominantly inherited axonal predominant neuropathy

3. HMSN 3 (also called Dejerine-Sottas disease), which is often inherited dominantly with onset in infancy or childhood, is characterized by extremely slow nerve conduction velocities resulting in loss of ambulatory milestones and more generalized neurologic deficit

4. HMSN 4, an autosomal recessive inherited demyelinating form that may also present with extraneural features, including facial dysmorphism and scoliosis, particularly those with HMSN 4C, the most frequent form of HMSN 4

5. HMSN 5, a form associated with spasticity, also known as "complex hereditary spastic paraplegia (HSP)"

 

Hereditary Motor Neuropathy:

dHMN are one of the major categories of peripheral inherited neuropathies and are characterized by length-dependent, slowly progressive motor neuropathies with variable nerve conduction velocities. The clinical phenotype is variable but includes progressive weakness and atrophy of the distal muscles, foot deformities, and decreased reflexes. There is significant phenotypic overlap with HMSN/CMT; however, sensory loss is usually absent in dHMN. dHMN are subdivided into 11 subtypes based on inheritance pattern and clinical features, and include types 1-7, dHMN plus pyramidal signs, X-linked, congenital distal spinal muscular atrophy, and Jerash type.

 

Hereditary Sensory and Autonomic Neuropathy:

HSAN, or HSN if autonomic dysfunction is absent, are one of the major categories of inherited peripheral neuropathies. They affect sensory and autonomic nerves and the hallmark feature is the presence of prominent small-fiber involvement. HSAN are subdivided into 5 groups based on age of onset, inheritance pattern, and clinical features:

1. HSAN 1 varieties (HSAN 1A-E) follow an autosomal dominant inheritance pattern with juvenile or adult onset, and severe sensory loss and autonomic dysfunction

2. HSAN 2-5 have an autosomal recessive inheritance pattern and are usually congenital

3. HSAN3, also known as familial dysautonomia or Rilay-Day syndrome, is characterized by prominent autonomic and small-fiber sensory involvement

4. HSAN 4 and 5 are characterized by insensitivity to pain and widespread autonomic disturbance, with HSAN 4 also featuring mental retardation.

 

Hereditary Spastic Paraplegia:

HSP is characterized by progressive lower extremity weakness and spasticity, and may present with prominent peripheral neuropathy as one of the complicated forms, also known as HMSN type 5. The complicated forms are associated with a variety of other neurological systemic abnormalities and usually follow an autosomal recessive inheritance pattern. The uncomplicated or pure form presents with lower limb weakness and spasticity, and is predominantly characterized by an autosomal dominant inheritance pattern.

 

SEPT9 Gene, Full Gene Analysis:

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder characterized by periods of severe pain involving the brachial plexus followed by muscle atrophy and weakness. These recurrent episodes can also be accompanied by decreased sensation and paresthesias. Individuals with this disease are generally symptom-free between pain attacks, though many experience lingering effects with repeated attacks. The pain episodes are frequently triggered by physical, emotional, or immunological stress. Less commonly, affected individuals can exhibit non-neurological features including short stature, skin folds, hypotelorism, and cleft palate.

 

Variants in the SEPT9 gene cause the clinical manifestations of HNA. SEPT9 is currently the only known gene associated with HNA, although approximately 15% of HNA families do not show linkage to this gene.

 

Given the considerable phenotypic overlap and the broad genetic heterogeneity of inherited peripheral neuropathies a comprehensive diagnostic genetic test is useful to establish the genetic cause in these clinical groups.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Some individuals who have involvement of 1 or more of the genes on the panel may have a variant that is not identified by the methods performed (eg, large deletions/duplications not targeted, promoter alterations, deep intronic alterations). The absence of a variant, therefore, does not eliminate the possibility of a hereditary peripheral neuropathy disorder. For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene variant in an affected family member.

 

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Technical Limitations:

In some cases, DNA variants of undetermined significance may be identified.

 

Due to the limitations of next-generation sequencing, small deletions and insertions may not be detected by this test. If a diagnosis of one of the syndromes on this panel is still suspected, contact a molecular genetic counselor at 800-533-1710 for more information regarding follow-up testing options.

 

Rare alterations exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

 

 

Evaluation Tools:

Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity clinically is currently not validated.

 

Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.

 

Reclassification of Variants-Policy:

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) At this time, it is not standard practice for the laboratory to systematically review “likely pathogenic" alterations or “variants of uncertain significance" that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards CS, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

2. Klein CJ, Duan X, Shy ME: Inherited neuropathies: Clinical overview and update. Muscle Nerve. 2013 Oct:48(4):604-622

3. Vallat JM, Mathis S, Funalot B: The various Charcot-Marie-Tooth diseases. Curr Opin Neurol. 2013 Oct;26(5):473-480

4. Rossor AM, Kalmar B, Greensmith L, Reilly MM: The distal hereditary motor neuropathies. J Neurol Neurosurg Psychiatry. 2012 Jan:83(1):6-14

5. Rotthier A, Baets J, Timmerman V, Janssens K: Mechanisms of disease in hereditary sensory and autonomic neuropathies. Nat Rev Neurol. 2012 Jan:8(2):73-85

6. Finsterer J, Loscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G: Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. J Neurol Sci. 2012 Jul:318(1-2):1-18

7. D'Amico A, Bertini E: Metabolic neuropathies and myopathies. Handb Clin Neurol. 2013;113:1437-1455

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence a variant in the genes analyzed. See Targeted Genes and Methodology Details for Peripheral Neuropathy Gene Panels in Special Instructions for details regarding the targeted genes for each test.

 

There may be regions of genes that cannot be effectively amplified and sequenced as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC)-rich content, and repetitive sequences.

 

Additionally, NGS is used to test for the presence of large deletions and duplications in a subset of genes. See Targeted Genes and Methodology Details for Peripheral Neuropathy Gene Panels in Special Instructions for details regarding the targeted genes analyzed for large deletions and duplications for each test.

 

Multiplex ligation-dependent probe amplification (MLPA), PCR, and Sanger sequencing is used to confirm alterations detected by NGS when appropriate.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Performed weekly

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 12 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81448 (if appropriate)

81405 (if appropriate)

81408 (if appropriate)

81407 (if appropriate)

81406 (if appropriate)

81479 (if appropriate)

81325 (if appropriate)

81403 (if appropriate)

81404 (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
NPPAN Peripheral Neuropathy Gene Panels In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
38195 Result Summary 50397-9
38196 Result 38179-8
38197 Interpretation 69047-9
38198 Additional Information 48767-8
38199 Specimen 31208-2
38200 Source 31208-2
38201 Released By 18771-6
MG112 Client Provided Sub-Panel 19145-2
MG121 Gene List ID or NA 48018-6
113190 Method 85069-3
113191 Disclaimer 62364-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
Obsolete Test 2022-12-06