Charcot-Marie-Tooth Neuropathy Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: NE1301

The Blueprint Genetics Charcot-Marie-Tooth Neuropathy Panel is an 86 gene test for genetic diagnostics of patients with clinical suspicion of Charcot-Marie-Tooth neuropathy.

Charcot-Marie-Tooth (CMT) neuropathy, also called hereditary motor/sensory neuropathy (HMSN), is the most common genetic cause of neuropathy. Prevalence is estimated to be 1:3300. CMT is characterized by broad genetic heterogeneity and can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. The prevalence of genetic subtypes differs in different countries and therefore the clinical utility of this comprehensive gene panel covering all inheritance patterns is high and serves all patients with clinical suspicion of CMT. Genetic counseling and family member testing is possible after the genetic cause of the disease is known. In rare cases the gene mutation causing CMT can be de novo.

About Charcot-Marie-Tooth Neuropathy

CMT neuropathy results from involvement of peripheral nerves that can affect the motor system and/or the sensory system. Individuals with CMT experience symmetric, slowly progressive distal motor neuropathy of the arms and legs usually beginning in the first to third decade and resulting in weakness and atrophy of the muscles in the feet and/or hands. Pes cavus foot deformity is common. CMT neuropathies can be divided to demyelination and axonal forms.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Charcot-Marie-Tooth Neuropathy Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
AARSEpileptic encephalopathy, early infantile, Charcot-Marie-Tooth diseaseAD/AR415
AIFM1DeafnessXL2221
AMACRAlpha-methylacyl-CoA racemase deficiency, Bile acid synthesis defectAR313
ARHGEF10Slowed nerve conduction velocityAD38
ATL1Spastic paraplegia, Neuropathy, hereditary sensoryAD2270
ATL3Neuropathy, hereditary sensoryAD12
ATP7AMenkes diseaseXL105335
BAG3Dilated cardiomyopathy (DCM), Myopathy, myofibrillarAD2148
BSCL2Lipodystrophy, congenital generalized, Encephalopathy, progressiveAR2043
C12ORF65Spastic paraplegia, Combined oxidative phosphorylation deficiencyAR9
CCT5Neuropathy, hereditary sensory, with spastic paraplegiaAR11
COX6A1Charcot-Marie-Tooth diseaseAR11
COX10*Leigh syndrome, Mitochondrial complex IV deficiencyAR3213
CTDP1Congenital cataracts, facial dysmorphism, and neuropathyAR11
DCAF8AD11
DCTN1Perry syndrome, Neuropathy, distal hereditary motorAD1140
DHTKD12-aminoadipic and 2-oxoadipic aciduria, Charcot-Marie-Tooth diseaseAD/AR615
DNM2Myopathy, Lethal akinesia and musculoskeletal abnormalities, with brain and retinal hemorrhages, Charcot-Marie-Tooth diseaseAD/AR2344
DNMT1Neuropathy, hereditary sensory, Cerebellar ataxia, deafness, and narcolepsyAD819
DSTNeuropathy, hereditary sensory and autonomicAR55
DYNC1H1Spinal muscular atrophy, Charcot-Marie-Tooth disease, Mental retardationAD3453
EGR2Neuropathy, Dejerine-Sottas disease, Charcot-Marie-Tooth diseaseAD/AR1223
FAM134BNeuropathy, hereditary sensory and autonomicAR85
FBLN5Cutis laxa, Macular degeneration, age-relatedAD/AR1321
FGD4Charcot-Marie-Tooth diseaseAR1224
FIG4Amyotrophic lateral sclerosis, Polymicrogyria, bilateral occipital, Yunis-Varon syndrome, Charcot-Marie-Tooth diseaseAD/AR1954
FXN*Friedreich ataxiaAR1165
GANGiant axonal neuropathyAR1273
GARSNeuropathy, distal hereditary motor, Charcot-Marie-Tooth diseaseAD932
GDAP1Charcot-Marie-Tooth diseaseAD/AR2885
GJB1Charcot-Marie-Tooth neuropathyXL66425
GNB4Charcot-Marie-Tooth diseaseAD23
GNEInclusion body myopathy, Nonaka myopathy, SialuriaAD/AR32193
HADHBTrifunctional protein deficiencyAR1055
HARSUsher syndromeAR610
HINT1Axonal neuropathy with neuromyotoniaAR712
HK1Hemolytic anemia, nonspherocytic, due to hexokinase deficiencyAR58
HSPB1Neuropathy, distal hereditary motor, Charcot-Marie-Tooth diseaseAD1235
HSPB8Charcot-Marie-Tooth disease, Distal hereditary motor neuronopathyAD36
IGHMBP2Spinal muscular atrophy, distal, Charcot-Marie-Tooth diseaseAR32113
INF2Glomerulosclerosis, Charcot-Marie-Tooth diseaseAD1159
KARSCharcot-Marie-Tooth diseaseAR614
KIF1ASpastic paraplegia, Neuropathy, hereditary sensory, Mental retardationAD/AR3527
KIF1BPheochromocytoma, NeuroblastomaAD69
KIF5ASpastic paraplegiaAD1035
LDB3Dilated cardiomyopathy (DCM), Myopathy, myofibrillarAD1011
LITAFCharcot-Marie-Tooth diseaseAD1013
LMNAHeart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford typeAD/AR183458
LRSAM1Charcot-Marie-Tooth diseaseAD/AR109
MARSInterstitial lung and liver diseaseAR89
MED25Basel-Vanagait-Smirin-Yosef syndrome, Charcot-Marie-Tooth diseaseAR14
MFN2Hereditary motor and sensory neuropathy, Charcot-Marie-Tooth diseaseAD/AR43198
MPZNeuropathy, Roussy-Levy syndrome, Dejerine-Sottas disease, Charcot-Marie-Tooth diseaseAD74235
MTMR2Charcot-Marie-Tooth diseaseAR721
MYOTMyopathy, myofibrillarAD813
NDRG1Charcot-Marie-Tooth diseaseAR53
NEFLCharcot-Marie-Tooth diseaseAD2136
NGFNeuropathy, hereditary sensory and autonomicAR26
NTRK1Insensitivity to pain, congenital, with anhidrosisAR2487
PDK3Charcot-Marie-Tooth diseaseXL12
PLEKHG5Spinal muscular atrophy, Charcot-Marie-Tooth diseaseAR77
PMP22Neuropathy, inflammatory demyelinating, Roussy-Levy syndrome, Dejerine-Sottas disease, Neuropathy, hereditary, with liability to pressurve palsies, Charcot-Marie-Tooth diseaseAD/AR39156
POLGPOLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndromeAD/AR71265
PRPS1*Deafness, Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndromeXL2226
PRXDejerine-Sottas disease, Charcot-Marie-Tooth diseaseAR1650
RAB7ACharcot-Marie-Tooth diseaseAD57
REEP1Spastic paraplegia, Distal hereditary motor neuronopathyAD1154
SACSSpastic ataxia, Charlevoix-SaguenayAR34220
SBF1Charcot-Marie-Tooth diseaseAR38
SBF2Charcot-Marie-Tooth diseaseAR1119
SCN9AParoxysmal extreme pain disorderAD/AR34102
SETXAtaxia with oculomotor apraxia, Amyotrophic lateral sclerosis, juvenile, Spinocerebellar ataxiaAD/AR25185
SH3TC2Mononeuropathy of the median nerve, Charcot-Marie-Tooth diseaseAR3576
SLC12A6Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome)AR1217
SMAD3Aneurysms-osteoarthritis syndrome, Loeys-Dietz syndromeAD2650
SPG11Spastic paraplegia, Amyotrophic lateral sclerosis, Charcot-Marie-Tooth diseaseAR107239
SPTLC1*Neuropathy, hereditary sensory and autonomicAD610
SPTLC2Hereditary sensory and autonomic neuropathyAD414
SURF1Leigh syndrome, Charcot-Marie-Tooth diseaseAR3198
TFGSpastic paraplegia, Hereditary motor and sensory neuropathy, proximalAR36
TRIM2Charcot-Marie-Tooth diseaseAR33
TRPV4Metatropic dysplasia, Spondyloepiphyseal dysplasia Maroteaux type, Parastremmatic dwarfism, Hereditary motor and sensory neuropathy, Spondylometaphyseal dysplasia Kozlowski type, Spinal muscular atrophy, Charcot-Marie-Tooth disease, Brachyolmia (autosomal dominant type), Familial Digital arthropathy with brachydactylyAD5371
TYMPMitochondrial DNA depletion syndromeAR9892
VCPAmyotrophic lateral sclerosis, Inclusion body myopathy with early-onset Paget disease, Charcot-Marie-Tooth diseaseAD1548
WNK1Neuropathy, hereditary sensory and autonomic, PseudohypoaldosteronismAD/AR1516
YARSCharcot-Marie-Tooth diseaseAD67
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive Charcot-Marie-Tooth neuropathy panel that covers classical genes associated with Charcot-Marie-Tooth neuropathy. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

Commonly used ICD-10 codes when ordering the Charcot-Marie-Tooth Neuropathy Panel

ICD-10Disease
G60.0Charcot-Marie-Tooth neuropathy

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.