Comprehensive Neuropathy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10427 AARS1 81479,81479 Order Options and Pricing
AIFM1 81479,81479
ATL1 81406,81479
ATP7A 81479,81479
BICD2 81479,81479
BSCL2 81406,81479
CCT5 81479,81479
COX6A1 81479,81479
DCTN1 81479,81479
DHTKD1 81479,81479
DNAJB2 81479,81479
DNM2 81479,81479
DNMT1 81479,81479
DYNC1H1 81479,81479
EGR2 81404,81479
ELP1 81479,81479
FBLN5 81479,81479
FGD4 81479,81479
FIG4 81406,81479
GAN 81479,81479
GARS1 81406,81479
GDAP1 81405,81479
GJB1 81403,81479
GNB4 81479,81479
HINT1 81479,81479
HK1 81479,81479
HSPB1 81404,81479
HSPB3 81479,81479
HSPB8 81479,81479
IGHMBP2 81479,81479
INF2 81406,81479
KARS1 81479,81479
KIF1A 81479,81479
KIF5A 81479,81479
LAS1L 81479,81479
LITAF 81404,81479
LMNA 81406,81479
LRSAM1 81479,81479
MARS1 81479,81479
MED25 81479,81479
MEGF10 81479,81479
MFN2 81406,81479
MPZ 81405,81479
MTMR2 81479,81479
NDRG1 81479,81479
NEFL 81405,81479
NGF 81479,81479
NTRK1 81479,81479
PDK3 81479,81479
PLEKHG5 81479,81479
PMP22 81325,81324
PRPS1 81479,81479
PRX 81405,81479
RAB7A 81405,81479
REEP1 81405,81479
RETREG1 81479,81479
SBF1 81479,81479
SBF2 81479,81479
SCN9A 81479,81479
SETX 81406,81479
SH3TC2 81406,81479
SLC12A6 81479,81479
SLC5A7 81479,81479
SPTLC1 81479,81479
SPTLC2 81479,81479
TFG 81479,81479
TRIM2 81479,81479
TRPV4 81479,81479
TTR 81404,81479
WNK1 81479,81479
YARS1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10427Genes x (71)81479 81324, 81325, 81403, 81404, 81405, 81406, 81479 $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

This comprehensive panel includes genes that are causative for Charcot-Marie-Tooth disease (CMT), hereditary motor neuropathies and hereditary sensory and autonomic neuropathies (HSAN). These inherited neuropathies of the peripheral nervous system are genetically and phenotypically heterogeneous.

Charcot Marie Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN) is a large group of inherited disorders of the peripheral nerves. The progressive degeneration of motor nerves results in weakness and atrophy of the distal muscles. The degeneration of sensory nerves leads to decreased sensation, tingling and numbness in the legs, feet, arms and hands and neuropathic pain. The age of onset varies from childhood to mid adulthood. Symptoms usually begin with weakness and atrophy in the muscles of the legs and feet. As the disease progresses, weakness and atrophy of the muscles of the arms and hands may occur. CMT is heterogeneous in regards to symptoms, severity and progression rate. Although the disease may lead to disability and respiratory difficulty, life expectancy is usually unaffected. Most common symptoms include foot deformity, loss of balance, hammertoes, foot drop, frequent tripping and falls, and reduced manual dexterity (Bird and Bird. 2015. PubMed ID: 20301532). Diagnosis is based on clinical features, family history, neurological examination, and electromyography (EMG) and nerve conduction velocity (NCV) findings. CMT affects approximately 1 in 3,300 people (Bird and Bird. 2015. PubMed ID: 20301532; Saporta et al. 2011. PubMed ID: 21280073). Demyelinating forms of CMT primarily affect the myelin sheath of the peripheral nerve and are characterized by slow nerve conduction velocities (NCV) of less than 38 m/s in upper limbs. Axonal forms of CMT primarily affect the axons of the peripheral nerves and are characterized by normal or almost normal NCV of greater than 38 m/s. Intermediate NCV of 25-45 m/s can be difficult to classify as axonal or demyelinating.

Hereditary sensory and autonomic neuropathy (HSAN) is a heterogeneous group of slowly-progressing neurological diseases characterized by progressive dysfunction of peripheral sensory nerves (Auer-Grumbach. 2013. PubMed ID: 23931820; Auer-Grumbach. 2008. PubMed ID: 18348718). Many patients with HSAN manifest loss of pain and temperature sensation which can lead to chronic skin ulcers, and even osteomyelitis and necrosis (Auer-Grumbach. 2013. PubMed ID: 23931820). HSAN affects approximately 1 in 25,000 people (Auer-Grumbach. 2013. PubMed ID: 23931820, Davidson et al. 2012. PubMed ID: 22302274).

Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of disorders characterized by progressive distal motor weakness and atrophy. The distribution of weakness is usually greater in the distal lower limbs than the upper limbs, and weakness of the toe extensor muscles is often the presenting sign. Nerve conduction velocities are generally normal in dHMN, and sensory impairment is not a feature of this disorder. Subtypes of dHMN can be differentiated to some extent based on age of onset, pattern of weakness, rate of progression, and appearance of additional complicating features. For discussions on classification, pathophysiology, and molecular genetics of dHMN see Rossor et al. 2012. PubMed ID: 22028385 and Drew et al. 2011. PubMed ID: 21902652.

Genetics

Charcot-Marie-Tooth can be inherited in an autosomal dominant, autosomal recessive or an X-linked manner. The MPZ, LITAF, NEFL, PMP22, FBLN5, MFN2, YARS1/YARS, RAB7, TRPV4, GARS1/GARS, HSPB1, HSPB8, INF2, GNB4, AARS1/AARS, DYNC1H1, LRSAM1, DHTKD1, MARS1/MARS, KIF5A genes are involved in autosomal dominant CMT. Autosomal recessive forms of CMT involve the LMNA, MED25, HINT1, HK1, TRIM2, MTMR2, SBF2, SBF1, SH3TC2, PRX, FGD4, FIG4, NDRG1, KARS1/KARS, CTDP1, PLEKHG5, IGHMBP2 and COX6A1 genes. Pathogenic variants in the EGR2, GDAP1, and DNM2 genes can exhibit both dominant and recessive inheritance. In cases of Dejerine-Sottas syndrome, the PMP22, MPZ, EGR2, and PRX genes can exhibit both dominant and recessive inheritance as well. Pathogenic variants in the GJB1, AIFM1, PRPS1, and PDK3 genes are inherited in an X-linked manner. Approximately 70% of CMT1 is caused by the recurrent 1.5 Mb duplication of chromosome 17p11.2 which includes the PMP22 gene (Bird and Bird. 2015. PubMed ID: 20301532; Li et al. 2013. PubMed ID: 23224996).

HSAN 1 is inherited in an autosomal dominant manner and can be caused by pathogenic variants in multiple genes including SPTLC1, SPTLC2, ATL1, and DNMT1. HSAN 2-5 typically exhibit an autosomal recessive form of inheritance. HSAN 2 is associated with FAM13B, KIF1A, SCN9A, and WNK1. HSAN 3-5 are caused by pathogenic variants in ELP1/IKBKAP, NTRK1, and NGFB, respectively. CCT5 pathogenic variants can cause another autosomal recessive type of HSNA which does not fit into the current five classifications.

Distal hereditary motor neuropathies can be inherited as autosomal dominant, autosomal recessive, or X-linked conditions. Genes that are involved in dominantly inherited dHMN include HSPB1, HSPB8, SETX, GARS1, BSCL2, SLC5A7, DCTN1, TRPV4, and REEP1. Recessively inherited forms of dHMN are caused by pathogenic variants in the IGHMBP2, GAN, and HINT1 genes. Two X-linked forms are also known (ATP7A and LAS1L).

See individual gene test descriptions for information on molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

A genetic etiology can be identified in approximately 50-70% of individuals with Charcot-Marie-Tooth Disease (CMT) (Saporta et al. 2011. PubMed ID: 21280073; Rossor et al. 2013. PubMed ID: 24018473). Specifically, a molecular diagnosis can be identified in approximately 80-85% of individuals with demyelinating neuropathy (CMT1), and a molecular diagnosis can be identified in approximately 25-35% of individuals with axonal neuropathy (CMT2) (Bird and Bird. 2015. PubMed ID: 20301532; Rossor et al. 2013. PubMed ID: 24018473). It is estimated that ~70% of all Charcot Marie Tooth Type 1 (CMT1) is due to the PMP22 1.5 Mb duplication, while only around 5% of CMT1 cases are due to point pathogenic variants (Bird and Bird. 2015. PubMed ID: 20301532). Only about 20% of patients with distal hereditary motor neuropathy or hereditary sensory and autonomic neuropathy will obtain a genetic diagnosis (Rossor et al. 2012. PubMed ID: 22028385; Rotthier et al. 2009. PubMed ID: 19651702). The sensitivity of this panel will vary based on the clinical phenotype of the patient.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.7% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Please note that for technical reasons, exon 8 of the INF2 gene is not currently included in this panel. Thus far, only exons 2 to 6, especially exons 2 to 4 that encode the diaphanous inhibitory domain (DID), have been reported to harbor pathogenic INF2 variants (Boyer et al. 2011. PubMed ID: 21258034; Barua et al. 2013. PubMed ID: 23014460; Human Gene Mutation Database).

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Any patient with clinical symptoms consistent with a peripheral neuropathy.

Diseases

Name Inheritance OMIM ID
Amyloidogenic Transthyretin Amyloidosis AD 105210
Andermann Syndrome AR 218000
Charcot-Marie-Tooth Disease Dominant Intermediate 3 AD 607791
Charcot-Marie-Tooth Disease Type 2B AR 600882
Charcot-Marie-Tooth Disease Type 2B1 AR 605588
Charcot-Marie-Tooth Disease Type 2B2 AR 605589
Charcot-Marie-Tooth Disease Type 2C AR 606071
Charcot-Marie-Tooth Disease Type 2D AR 601472
Charcot-Marie-Tooth Disease Type 2E AR 607684
Charcot-Marie-Tooth Disease Type 2F AR 606595
Charcot-Marie-Tooth Disease Type 2I AR 607677
Charcot-Marie-Tooth Disease Type 2J AR 607736
Charcot-Marie-Tooth Disease Type 2K AR 607831
Charcot-Marie-Tooth Disease, Axonal, Type 2O AR 614228
Charcot-Marie-Tooth Disease, Axonal, With Vocal Cord Paresis, Autosomal Recessive AR 607706
Charcot-Marie-Tooth Disease, Dominant Intermediate B AD 606482
Charcot-Marie-Tooth Disease, Dominant Intermediate C AD 608323
Charcot-Marie-Tooth Disease, Dominant Intermediate E AD 614455
Charcot-Marie-Tooth Disease, Dominant Intermediate F AD 615185
Charcot-Marie-Tooth Disease, Recessive Intermediate A AR 608340
Charcot-Marie-Tooth Disease, Recessive Intermediate B AR 613641
Charcot-Marie-Tooth Disease, Recessive Intermediate C AR 615376
Charcot-Marie-Tooth Disease, Recessive Intermediate D AR 616039
Charcot-Marie-Tooth Disease, Type 1A AD 118220
Charcot-Marie-Tooth Disease, Type 1D AD 607678
Charcot-Marie-Tooth Disease, Type 1E AD 118300
Charcot-Marie-Tooth Disease, Type 1F AD 607734
Charcot-Marie-Tooth Disease, Type 2A2 AR 609260
Charcot-Marie-Tooth Disease, Type 2L AR 608673
Charcot-Marie-Tooth Disease, Type 2N AR 613287
Charcot-Marie-Tooth Disease, Type 2Q AD 615025
Charcot-Marie-Tooth Disease, Type 2R XL 615490
Charcot-Marie-Tooth Disease, Type 2S AR 616155
Charcot-Marie-Tooth Disease, Type 2T AR 616233
Charcot-Marie-Tooth Disease, Type 2U AD 616280
Charcot-Marie-Tooth Disease, Type 3 AR, AD 145900
Charcot-Marie-Tooth Disease, Type 4A AR 214400
Charcot-Marie-Tooth Disease, Type 4B1 AR 601382
Charcot-Marie-Tooth Disease, Type 4B2 AR 604563
Charcot-Marie-Tooth Disease, Type 4B3 AR 615284
Charcot-Marie-Tooth Disease, Type 4C AR 601596
Charcot-Marie-Tooth Disease, Type 4D AR 601455
Charcot-Marie-Tooth Disease, Type 4E AR 605253
Charcot-Marie-Tooth Disease, Type 4F AR 614895
Charcot-Marie-Tooth Disease, Type 4H AR 609311
Charcot-Marie-Tooth Disease, Type 4J AR 611228
Charcot-Marie-Tooth Disease, Type Ib AD 118200
Charcot-Marie-Tooth Disease, Type IC AD 601098
Charcot-Marie-Tooth Disease, X-Linked Dominant, 1 XL 302800
Charcot-Marie-Tooth Disease, X-linked Dominant, 6 AR 300905
Charcot-Marie-Tooth Disease, X-Linked Recessive, Type 5 XL 311070
Charcot-Marie-Toothe Disease, Type 2P AD,AR 614436
Cowchock Syndrome XL 310490
Distal Hereditary Motor Neuronopathy Type 2A AD 158590
Distal Hereditary Motor Neuronopathy Type 2B AD 608634
Distal Hereditary Motor Neuronopathy Type 5 AD 600794
Familial Dysautonomia AR 223900
Giant Axonal Neuropathy AD 256850
Hereditary Insensitivity To Pain With Anhidrosis AR 256800
Indifference To Pain, Congenital, Autosomal Recessive AR 243000
Myopathy, Early-Onset, Areflexia, Respiratory Distress, And Dysphagia AR 614399
Neuromyotonia and axonal neuropathy, autosomal recessive AR 137200
Neuronopathy, Distal Hereditary Motor, Type VIIB AD 607641
Neuronopathy, Distal Hereditary Motor, Type IIC AD 613376
Neuronopathy, Distal Hereditary Motor, Type VB AD 614751
Neuronopathy, Distal Hereditary Motor, Type VIIA AR 158580
Neuropathy, Hereditary Motor and Sensory, Okinawa Type AD 604484
Neuropathy, Hereditary Motor and Sensory, Russe Type AR 605285
Neuropathy, Hereditary Motor and Sensory, Type VIA AD 601152
Neuropathy, Hereditary Sensory And Autonomic, Type 1A AD 162400
Neuropathy, Hereditary Sensory And Autonomic, Type IC AR 613640
Neuropathy, Hereditary Sensory And Autonomic, Type IIA AR 201300
Neuropathy, Hereditary Sensory And Autonomic, Type IIB AR 613115
Neuropathy, Hereditary Sensory And Autonomic, Type V AR 608654
Neuropathy, Hereditary Sensory, Type ID AD 613708
Neuropathy, Hereditary Sensory, Type IE AD 614116
Neuropathy, Hereditary Sensory, Type IIC AR 614213
Neuropathy, Hereditary Sensory, With Spastic Paraplegia AR 256840
Neuropathy, Hereditary, with or without Age-Related Macular Degeneration AD 608895
Spinal Muscular Atrophy, Distal, X-Linked 3 XL 300489
Spinal Muscular Atrophy, Lower Extremity-Predominant, 2 AD 615290
Spinocerebellar Ataxia Autosomal Recessive 1 AR 606002

Related Test

Name
PGxome®

Citations

  • Auer-Grumbach. 2008. PubMed ID: 18348718
  • Auer-Grumbach. 2013. PubMed ID: 23931820
  • Barua et al. 2013. PubMed ID: 23014460
  • Bird and Bird. 2015. PubMed ID: 20301532
  • Boyer et al. 2011. PubMed ID: 21258034
  • Davidson et al. 2012. PubMed ID: 22302274
  • Drew et al. 2011. PubMed ID: 21902652
  • Human Gene Mutation Database (Bio-base).
  • Li et al. 2013. PubMed ID: 23224996
  • Rossor et al. 2012. PubMed ID: 22028385
  • Rossor et al. 2013. PubMed ID: 24018473
  • Rotthier et al. 2009. PubMed ID: 19651702
  • Saporta et al. 2011. PubMed ID: 21280073

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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  • The test can be added to your online orders in the Summary and Pricing section.
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Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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