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  • Alternate specimens:
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  1. Test Catalog
  2. Invitae Comprehensive Neuropathies Panel

Invitae Comprehensive Neuropathies Panel

Test description

The Invitae Comprehensive Neuropathies Panel analyzes up to 83 genes associated with hereditary neuropathies including Charcot-Marie-Tooth disease, hereditary motor neuropathies and hereditary sensory and autonomic neuropathies, as well as several other genes associated with rare neuropathies. These genes were curated based on the available evidence to date to provide a comprehensive test for these conditions.

This test is Invitae’s broadest neuropathy panel. Given the clinical overlap between different neuropathies, comprehensive testing enables a more efficient evaluation of multiple conditions using a single test. It is particularly helpful if the inheritance pattern is unclear from the individual’s family history, the individual/family has an unusual presentation or family history, or other more targeted panels have been evaluated and are negative. Individuals with clinical signs and symptoms of sensory and/or motor neuropathy may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance, help determine which relatives are at risk, or qualify affected individuals to enroll in certain clinical trials.

Genes tested

Primary panel

AARS AIFM1 ATL1 ATL3 ATP7A BICD2 BSCL2 CHCHD10 DCTN1 DNAJB2 DNM2 DNMT1 DST DYNC1H1 EGR2 ELP1 FBXO38 FGD4 FIG4 GAN GARS GDAP1 GJB1 GNB4 HARS HINT1 HSPB1 HSPB8 IGHMBP2 INF2 KIF1A LITAF LMNA LRSAM1 MED25 MFN2 MORC2 MPZ MTMR2 NDRG1 NEFL NGF NTRK1 PDK3 PLEKHG5 PMP22 PRPS1 PRX RAB7A REEP1 RETREG1 SBF2 SCN11A SCN9A SH3TC2 SIGMAR1 SLC25A46 SLC52A2 SLC52A3 SLC5A7 SPG11 SPTLC1 SPTLC2 TFG TRIM2 TRPV4 TTR UBA1 VAPB VRK1 WNK1 YARS

Add-on Preliminary-evidence Genes for Neuropathies

CCT5 FLRT1 HSPB3 LAS1L MARS PRDM12 SCN10A SETX SURF1

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

Add-on Spinal Muscular Atrophy Genes

SMN1, SMN2

SMN1-related spinal muscular atrophy (SMA) is the most common form of proximal SMA and is one of the most common autosomal recessive diseases. It presents differently than distal spinal muscular atrophy (DSMA), also known as dHMN or HMN, which is characterized by slowly progressive symmetrical and predominantly distal limb weakness. Depending on the clinical presentation of the patient, clinicians may wish to broaden analysis by including these genes. These genes can be added at no additional charge.

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Primary panel (72 genes)

AARS AIFM1 ATL1 ATL3 ATP7A BICD2 BSCL2 CHCHD10 DCTN1 DNAJB2 DNM2 DNMT1 DST DYNC1H1 EGR2 ELP1 FBXO38 FGD4 FIG4 GAN GARS GDAP1 GJB1 GNB4 HARS HINT1 HSPB1 HSPB8 IGHMBP2 INF2 KIF1A LITAF LMNA LRSAM1 MED25 MFN2 MORC2 MPZ MTMR2 NDRG1 NEFL NGF NTRK1 PDK3 PLEKHG5 PMP22 PRPS1 PRX RAB7A REEP1 RETREG1 SBF2 SCN11A SCN9A SH3TC2 SIGMAR1 SLC25A46 SLC52A2 SLC52A3 SLC5A7 SPG11 SPTLC1 SPTLC2 TFG TRIM2 TRPV4 TTR UBA1 VAPB VRK1 WNK1 YARS

Panel details and technical assay limitations
Add-on Preliminary-evidence Genes for Neuropathies (9 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

CCT5 FLRT1 HSPB3 LAS1L MARS PRDM12 SCN10A SETX SURF1

Panel details and technical assay limitations
Add-on Spinal Muscular Atrophy Genes (2 genes)

SMN1-related spinal muscular atrophy (SMA) is the most common form of proximal SMA and is one of the most common autosomal recessive diseases. It presents differently than distal spinal muscular atrophy (DSMA), also known as dHMN or HMN, which is characterized by slowly progressive symmetrical and predominantly distal limb weakness. Depending on the clinical presentation of the patient, clinicians may wish to broaden analysis by including these genes. These genes can be added at no additional charge.

SMN1, SMN2

Panel details and technical assay limitations

Clinical information

Hereditary neuropathies can manifest as a combination of sensory and motor neuropathy, isolated motor neuropathy or isolated sensory neuropathy (sometimes with autonomic neuropathy).

Charcot-Marie-Tooth disease
Charcot-Marie-Tooth (CMT) disease is a group of hereditary neuropathies characterized by progressive muscle weakness and sensory loss in the arms and legs. Individuals in the early stages of the disease often present with clumsiness due to numbness in the feet. As the disease progresses, the lack of nerve conduction to the extremities can also result in depressed tendon reflexes, muscle atrophy—especially at the ankles and hands, and foot deformities such as high, arched feet or hammertoes. Symptoms are caused by the impairment of the ability of peripheral nerves to conduct signals throughout the body, which results in reduced motor control and sensation in the arms and legs, especially at the ankles and wrists. Different subtypes of CMT are caused by different types of peripheral nerve abnormalities: abnormalities in the peripheral nerve axons (axonal types), abnormalities in the myelin sheath that insulates peripheral nerve axons (demyelinating types), or (rarely) both types of abnormalities (intermediate). Nerve conduction studies can be used in combination with inheritance pattern to determine the type of CMT (CMT1, 2, 4, X, or dominant intermediate), but genetic testing is needed to identify the specific subtype (e.g., CMT1A versus CMT1B).

Hereditary motor neuropathies
Hereditary motor neuropathies (HMNs), in some cases referred to as spinal muscular atrophies (SMAs), are a clinically and genetically heterogeneous group of disorders characterized by loss of motor neurons within the spinal cord, resulting in weakness and muscle wasting. The weakness and wasting is primarily distal, but in some cases can be proximal or combined proximal/distal. Typical clinical findings include slowly progressive muscle weakness and wasting. Onset of symptoms varies from the prenatal period to adulthood. Some forms of HMN also have minor involvement of the sensory neurons. Other features are variable depending on the causative gene, and may include vocal cord paralysis, facial weakness, pyramidal signs, and arthrogryposis. Many genes associated with HMN can also cause other forms of neuropathy with overlapping symptoms, such as Charcot-Marie-Tooth disease.

Hereditary sensory and autonomic neuropathies
Hereditary sensory and autonomic neuropathies (HSAN) are a clinically heterogeneous group of disorders that predominantly affect the sensory neurons of the peripheral nervous system, with or without autonomic neuron involvement. Loss of sensory neuron function can lead to complications including frequent injuries, ulcerations, bone infections and amputation. Possible autonomic features include anhidrosis, hyperhidrosis, abnormal blood pressure fluctuations, and gastrointestinal issues. Sensory abnormalities are often more significant than autonomic abnormalities. Motor neuron involvement may also occur in some individuals. Depending on the causative gene, other findings may also be present, such as hearing loss, gait impairment, decreased tendon reflexes, hypotonia, delayed development, and congenital insensitivity to pain. Age of onset varies from infancy to adulthood.

Small fiber neuropathy
Small fiber neuropathy (SFNP) is characterized by neuropathic burning or stabbing pain that typically occurs in the distal lower extremities and presents between adolescence and adulthood. Pain may be accompanied by autonomic symptoms such as heart palpitations, dry eyes, dry mouth, and/or orthostatic hypotension-induced dizziness. Affected individuals typically experience heightened sensitivity to pain in general, but cannot feel pain concentrated in very small areas, such as a pinprick. Individuals may also have other sensory issues, such as the reduced ability to differentiate between hot and cold temperatures. Symptoms of this painful neuropathy may worsen over time and extend to include other parts of the body in addition to the hands and feet. The principal nerve biopsy finding consists of decreased small nerve fiber diameter.

Riboflavin transporter deficiency neuronopathy
Riboflavin transporter deficiency neuronopathy is a neurodegenerative disorder characterized by progressive axonal sensorimotor neuropathy. Clinical features of this disorder include bulbar palsy (facial weakness, drooping eyelids, difficulty speaking and swallowing), weakness and distal muscle atrophy in the limbs (typically more severe in the upper than lower limbs), respiratory distress due to diaphragmatic weakness, and gait ataxia. Sensorineural hearing loss occurs in many individuals and may be the presenting symptom. Historically, the clinical subtype of riboflavin transporter deficiency neuronopathy that includes hearing loss has been called Brown-Vialetto-Van Laere syndrome, and the clinical subtype that does not include hearing loss has been called Fazio-Londe disease. Onset of symptoms typically occurs in early childhood; however, genetically confirmed early-adult onset cases have been reported. Since the discovery of the underlying molecular defect in this disorder, high-dose riboflavin supplementation has been reported to be an effective treatment.

Familial amyloid polyneuropathy
Familial amyloid polyneuropathy (FAP), or transthyretin amyloidosis, is characterized by amyloidosis, the buildup of abnormal amyloid protein deposits in the body. FAP can present with progressive axonal sensory autonomic and motor neuropathy and infiltrative cardiomyopathy. Additional features may include conduction block, nephropathy, vitreous opacities, or neurological symptoms related to CNS amyloidosis. Transthyretin amyloidosis can also be an acquired condition, due to age-related deposition of TTR, referred to as senile systemic amyloidosis.

Spinal muscular atrophy
Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by the loss of motor neurons within the spinal cord, which results in progressive muscle weakness and atrophy. Other features of SMA may include muscle fasciculations, tremor, poor weight gain, sleeping difficulties, pneumonia, scoliosis, joint contractures, and congenital heart disease. Four clinical SMA subtypes have been distinguished: severe infantile acute SMA type I (also referred to as Werdnig-Hoffman disease), infantile chronic SMA type II, juvenile SMA type III (also referred to as Wohlfard-Kugelberg-Welander disease), and adult-onset SMA type IV.

The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. For each condition, the table below shows the percentage of clinical cases in which a pathogenic variant is expected through analysis of the genes on this panel. See example below.

Sensitivity by clinical conditionGenesReferences
60 – 80% of Charcot-Marie-Tooth Disease AARS, AIFM1, BSCL2, DNAJB2, DNM2, DYNC1H1, EGR2, FGD4, FIG4, GARS, GDAP1, GJB1, GNB4, HARS, HINT1, HSPB1, HSPB8, IGHMBP2, INF2, LITAF, LMNA, LRSAM1, MED25, MFN2, MORC2, MPZ, MTMR2, MPZ, MTMR2, NDRG1, NEFL, PDK3, PLEKHG5, PMP22, PRPS1, PRX, RAB7A, SBF2, SH3TC2, SPG11, TFG, TRIM2, TRPV4, YARS, MARS, SLC25A46, SURF1 PMID: 21280073, 20301532
Depending on subtype and ancestry of the patient, up to 99% of Hereditary Sensory and Autonomic Neuropathy (ELP1, formerly known as IKBKAP) ATL1, ATL3, DNMT1, DST, ELP1, KIF1A, NGF, NTRK1, RAB7A, SCN11A, SCN9A, SPTLC1, SPTLC2, WNK1, CCT5, PRDM12, RETREG1 (formerly known as FAM134B) PMID: 21194679, 24459106, 21532572, 22522446, 19838196,  11179008, 21820098,  14976160,  8696348,  12545426,   24036948,  17167479, 11242114, 15060842,  16399879, 26005867
8% – 20% of Hereditary Motor Neuron Disease ATP7A, BICD2, BSCL2, CHCHD10, DCTN1, DNAJB2, DYNC1H1, FBXO38, GARS, HINT1, HSPB1, HSPB8, IGHMBP2, PLEKHG5, REEP1, SLC5A7, TRPV4, UBA1, VAPB, HSPB3, SIGMAR1, VRK1 PMID: 18325928, 22028385    
30% of Small Fiber Neuropathy SCN9A, SCN10A PMID:21698661, 23115331
>99% of Riboflavin Transporter Deficiency Neuropathy SLC52A2, SLC52A3 PMID: 26072523, 24253200, 22740598
>99% of Hereditary Transthyretin Amyloidosis TTR PMID:25299040, 25044787, 25299040
>99% of Spinal Muscular Atrophy SMN1, SMN2 PMID:20301526, 26515624, 17761659, 10679938, 11839954

Neuropathies can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.

Hereditary neuropathies are a diverse group of disorders, and the penetrance (the chance that someone who inherits a genetic predisposition will go on to manifest the disorder) is not always known. Where known, penetrance is usually high, but is age age-dependent, and there may be variability in age of onset and symptom severity. Nonpenetrance is reported for some genes, including SMN1, ATL1 and SPTLC1.

Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system. Overall prevalence of CMT is usually reported as 1 in 2,500, although several more recent epidemiological studies reported prevalences of CMT ranging from 1 in 1,214 (in Norway) to 1 in 6,500 (in the United Kingdom). It is possible these figures may be an underestimation of the prevalence of CMT due to under-diagnosis of mild or late-onset cases. Hereditary motor neuropathies are a rare group of disorders, and the overall prevalence of these conditions is unknown. The prevalence of SMN1-related SMA is estimated to be <2 per 100,000 of the general population (PMID: 745211). The overall prevalence of HSAN is unknown, although frequencies of different forms of HSAN can vary by ethnicity. Familial dysautonomia (HSAN3) is more common in the Ashkenazi Jewish population, with an estimated incidence of 1 in 3,700. The prevalence of WNK1-associated HSAN2A is increased in the French Canadian population.

Hereditary neuropathies are a heterogeneous group of disorders. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform family planning.

  1. Guelly, C, et al. Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I. Am. J. Hum. Genet. 2011; 88(1):99-105. PMID: 21194679
  2. Klein, CJ, et al. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat. Genet. 2011; 43(6):595-600. PMID: 21532572
  3. Cox, JJ, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006; 444(7121):894-8. PMID: 17167479
  4. Lafreniere, RG, et al. Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates. Am. J. Hum. Genet. 2004; 74(5):1064-73. PMID: 15060842
  5. Dierick, I, et al. Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study. Brain. 2008; 131(Pt 5):1217-27. PMID: 18325928
  6. Rossor, AM, et al. The distal hereditary motor neuropathies. J. Neurol. Neurosurg. Psychiatr. 2012; 83(1):6-14. PMID: 22028385
  7. Prior, TW, Russman, BS. Spinal Muscular Atrophy. 2000 Feb 24. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301526
  8. Saporta, AS, et al. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann. Neurol. 2011; 69(1):22-33. PMID: 21280073
  9. Indo, Y, et al. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat. Genet. 1996; 13(4):485-8. PMID: 8696348
  10. Wirth, B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum. Mutat. 2000; 15(3):228-37. PMID: 10679938
  11. Slaugenhaupt, SA, et al. Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am. J. Hum. Genet. 2001; 68(3):598-605. PMID: 11179008
  12. Dawkins, JL, et al. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat. Genet. 2001; 27(3):309-12. PMID: 11242114
  13. Mailman, MD, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet. Med. 2002; 4(1):20-6. PMID: 11839954
  14. Verhoeven, K, et al. Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am. J. Hum. Genet. 2003; 72(3):722-7. doi: 10.1086/367847. PMID: 12545426
  15. Einarsdottir, E, et al. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum. Mol. Genet. 2004; 13(8):799-805. PMID: 14976160
  16. Bouhouche, A, et al. Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. J. Med. Genet. 2006; 43(5):441-3. PMID: 16399879
  17. Wang, CH, et al. Consensus statement for standard of care in spinal muscular atrophy. J. Child Neurol. 2007; 22(8):1027-49. PMID: 17761659
  18. Kurth, I, et al. Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat. Genet. 2009; 41(11):1179-81. PMID: 19838196
  19. Bird, TD. Charcot-Marie-Tooth Hereditary Neuropathy Overview. 1998 Sep 28. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1358/ PMID: 20301532
  20. Faber, CG, et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann. Neurol. 2012; 71(1):26-39. PMID: 21698661
  21. Rivière, JB, et al. KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am. J. Hum. Genet. 2011; 89(2):219-30. PMID: 21820098
  22. Edvardson, S, et al. Hereditary sensory autonomic neuropathy caused by a mutation in dystonin. Ann. Neurol. 2012; 71(4):569-72. PMID: 22522446
  23. Johnson, JO, et al. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. Brain. 2012; 135(Pt 9):2875-82. PMID: 22740598
  24. Faber, CG, et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc. Natl. Acad. Sci. U.S.A. 2012; 109(47):19444-9. PMID: 23115331
  25. Leipold, E, et al. A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nat. Genet. 2013; 45(11):1399-404. PMID: 24036948
  26. Foley, AR, et al. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014; 137(Pt 1):44-56. PMID: 24253200
  27. Kornak, U, et al. Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. Brain. 2014; 137(Pt 3):683-92. PMID: 24459106
  28. Rowczenio, DM, et al. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum. Mutat. 2014; 35(9):E2403-12. doi: 10.1002/humu.22619. PMID: 25044787
  29. Ferreira, C, et al. Barth Syndrome. 2014 Oct 09. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK247162/ PMID: 25299040
  30. Chen, YC, et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat. Genet. 2015; 47(7):803-8. PMID: 26005867
  31. Manole, A, Houlden, H. Riboflavin Transporter Deficiency Neuronopathy. 2015 Jun 11. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 26072523
  32. Kolb, SJ, Kissel, JT. Spinal Muscular Atrophy. Neurol Clin. 2015; 33(4):831-46. PMID: 26515624

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AARS NM_001605.2
AIFM1 NM_004208.3
ATL1 NM_015915.4
ATL3 NM_015459.4
ATP7A NM_000052.6
BICD2 NM_001003800.1
BSCL2 NM_032667.6
CCT5 NM_012073.3
CHCHD10 NM_213720.2
DCTN1 NM_004082.4
DNAJB2 NM_001039550.1
DNM2 NM_001005360.2
DNMT1 NM_001130823.1
DST NM_001723.5; NM_015548.4
DYNC1H1 NM_001376.4
EGR2 NM_000399.3
ELP1 NM_003640.3
FBXO38 NM_030793.4
FGD4 NM_139241.3
FIG4 NM_014845.5
FLRT1 NM_013280.4
GAN NM_022041.3
GARS NM_002047.2
GDAP1 NM_018972.2
GJB1 NM_000166.5
GNB4 NM_021629.3
HARS NM_002109.5
HINT1 NM_005340.6
HSPB1 NM_001540.3
HSPB3 NM_006308.2
HSPB8 NM_014365.2
IGHMBP2 NM_002180.2
INF2 NM_022489.3
KIF1A NM_004321.6
LAS1L NM_031206.4
LITAF NM_004862.3
LMNA NM_170707.3
LRSAM1 NM_138361.5
MARS NM_004990.3
MED25 NM_030973.3
MFN2 NM_014874.3
MORC2 NM_001303256.2
MPZ NM_000530.6
MTMR2 NM_016156.5
NDRG1 NM_006096.3
NEFL NM_006158.4
NGF NM_002506.2
NTRK1 NM_001012331.1
PDK3 NM_001142386.2
PLEKHG5 NM_020631.4
PMP22 NM_000304.3
PRDM12 NM_021619.2
PRPS1 NM_002764.3
PRX NM_181882.2
RAB7A NM_004637.5
REEP1 NM_022912.2
RETREG1 NM_001034850.2
SBF2 NM_030962.3
SCN10A NM_006514.3
SCN11A NM_014139.2
SCN9A NM_002977.3
SETX NM_015046.5
SH3TC2 NM_024577.3
SIGMAR1 NM_005866.3
SLC25A46 NM_138773.2
SLC52A2 NM_024531.4
SLC52A3 NM_033409.3
SLC5A7 NM_021815.2
SMN1, SMN2* SMN1: NM_000344.3, SMN2: NM_017411.3
SPG11 NM_025137.3
SPTLC1 NM_006415.3
SPTLC2 NM_004863.3
SURF1 NM_003172.3
TFG NM_006070.5
TRIM2 NM_001130067.1
TRPV4 NM_021625.4
TTR NM_000371.3
UBA1 NM_003334.3
VAPB NM_004738.4
VRK1 NM_003384.2
WNK1 NM_213655.4
YARS NM_003680.3

SMN1, SMN2: The SMN1 gene is identical to the SMN2 gene with the exception of exon 8 (typically referred to as exon 7). This assay unambiguously detects SMN1 exon 8 copy number and sequence variants. Sequence variants outside of exon 8 will also be detected, but this assay cannot determine whether the variant is located in SMN1 or SMN2. SMN2 exon 8 copy number will be reported for individuals with a positive result in SMN1. CNVs of exons 1-7 of SMN1 or SMN2 (typically referred to as exons 1-6 in the literature) will not be reported. This assay cannot detect silent carriers (individuals that have 2 functional copies of SMN1 on one chromosome and zero copies on the other). Therefore a negative result for carrier testing greatly reduces but does not eliminate the chance that a person is a carrier. For individuals with 2 copies of SMN1, the residual risk of being a carrier has been reported to be 1 in 121 in African Americans, 1 in 345 in Ashkenazi Jewish individuals, 1 in 628 in Asians, 1 in 632 in Caucasians, and 1 in 1061 in Hispanic individuals (PMID: 23788250). The SMA-STAT test does not detect sequence variants in SMN1 or SMN2, and therefore cannot be used to identify compound heterozygotes.

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References

  1. Bird, TD. Charcot-Marie-Tooth Hereditary Neuropathy Overview. 1998 Sep 28. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1358/ PMID: 20301532
  2. Bouhouche, A, et al. Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. J. Med. Genet. 2006; 43(5):441-3. PMID: 16399879
  3. Chen, YC, et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat. Genet. 2015; 47(7):803-8. PMID: 26005867
  4. Cox, JJ, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006; 444(7121):894-8. PMID: 17167479
  5. Dawkins, JL, et al. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat. Genet. 2001; 27(3):309-12. PMID: 11242114
  6. Dierick, I, et al. Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study. Brain. 2008; 131(Pt 5):1217-27. PMID: 18325928
  7. Edvardson, S, et al. Hereditary sensory autonomic neuropathy caused by a mutation in dystonin. Ann. Neurol. 2012; 71(4):569-72. PMID: 22522446
  8. Einarsdottir, E, et al. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum. Mol. Genet. 2004; 13(8):799-805. PMID: 14976160
  9. Faber, CG, et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann. Neurol. 2012; 71(1):26-39. PMID: 21698661
  10. Faber, CG, et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc. Natl. Acad. Sci. U.S.A. 2012; 109(47):19444-9. PMID: 23115331
  11. Ferreira, C, et al. Barth Syndrome. 2014 Oct 09. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK247162/ PMID: 25299040
  12. Foley, AR, et al. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014; 137(Pt 1):44-56. PMID: 24253200
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