Invitae Charcot-Marie-Tooth Disease Autosomal Dominant Panel


Test description

The Invitae Charcot-Marie-Tooth Disease Autosomal Dominant Panel analyzes up to 25 genes associated with Charcot-Marie-Tooth (CMT) disease, a hereditary neuropathy. These genes were curated based on the available evidence to date to provide a comprehensive test for genes associated with autosomal dominant CMT. Individuals with clinical signs and symptoms of CMT may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance, help determine which relatives are at risk, or qualify affected patients to enroll in certain clinical trials.

This test covers genes associated with a dominant inheritance pattern (i.e., multiple generations are affected and male-to-male can be present). Some clinicians may choose to order this test instead of the broader Invitae Charcot-Marie-Tooth Disease Comprehensive Panel to decrease the chance of detecting variants of uncertain significance.

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Primary panel (24 genes)


INF2: Readthrough analysis is not offered for exon 8.

Add-on preliminary-evidence genes (1 gene)

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.


Alternative tests to consider

The genes on this panel can also be ordered as part of a broader panel to comprehensively test for Charcot-Marie-Tooth disease. Depending on the individual’s clinical and family history, these broader panels may be appropriate.

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 can be caused by abnormalities in the myelin sheath that insulates peripheral nerve axons (demyelinating, also known as CMT type 1), abnormalities in the peripheral nerve axons (axonal, also known as CMT type 2), or (rarely) abnormalities in both (intermediate). This test is specific for subtypes of CMT that can be inherited in an autosomal dominant pattern (CMT1, CMT2 and dominant intermediate).

GeneSubtypeAdditional information
AARS CMT2N axonal neuropathy
BSCL2 CMT2 axonal neuropathy
DNM2 DI-CMTB intermediate nerve conduction velocities
DYNC1H1 CMT2O axonal neuropathy
EGR2 CMT1D, CMT4E demyelinating neuropathy
GARS CMT2D axonal neuropathy
GDAP1 CMT2H/2K, CMT4A variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy, accounts for ~1% of CMT
GNB4 DI-CMTF variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy
HARS CMT2W axonal neuropathy
HSPB1 CMT2F axonal neuropathy
HSPB8 CMT2L axonal neuropathy
INF2 DI-CMTE intermediate nerve conduction velocities
LITAF CMT1C demyelinating neuropathy
LMNA CMT2B1 axonal neuropathy
LRSAM1 CMT2P axonal neuropathy
MARS* CMT2U axonal neuropathy
MFN2 CMT2A2 axonal neuropathy, common cause of dominant CMT
MORC2 CMT2Z axonal neuropathy
MPZ CMT1B, CMT2I, CMT2J, DI-CMTD variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy, common cause of dominant CMT
NEFL CMT2E, CMT1F variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy
PMP22 CMT1A, CMT1E, HNPP demyelinating neuropathy, common cause of dominant CMT
RAB7A CMT2B axonal neuropathy
TFG HMNSO axonal neuropathy
TRPV4 CMT2C axonal neuropathy
YARS DI-CMTC variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy

*Preliminary-evidence genes

This multi-gene panel covers the most common genetic causes of autosomal dominant CMT, including PMP22, MPZ, and MFN2—three genes that account for 50%-75% of all autosomal dominant CMT cases. Genes that have been identified as rare causes of autosomal dominant CMT are also included in this test.

The CMT subtypes included in this test are all inherited in an autosomal dominant pattern. Some of these subtypes (EGR2, GDAP1, LMNA, LRSAM1, MFN2, NEFL) can also be inherited in an autosomal recessive pattern.

Individuals who have inherited a genetic variant that causes autosomal dominant CMT are extremely likely to develop symptoms at some point in their lifetimes; however, the age of onset and the severity of symptoms are difficult to predict. Significant intra-family variability with respect to age of onset, symptoms, and disease progression has been observed.

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.

Subtypes of CMT can be partially distinguished by inheritance pattern and the use of nerve conduction studies. These different subtypes can be associated with different disease severities and symptoms, but the clinical presentations vary by individual and it is difficult to distinguish the subtypes based on presentation alone. Genetic testing enables clinicians to more precisely diagnose the specific subtype of CMT.

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AARS NM_001605.2
BSCL2 NM_032667.6
DNM2 NM_001005360.2
DYNC1H1 NM_001376.4
EGR2 NM_000399.3
GARS NM_002047.2
GDAP1 NM_018972.2
GNB4 NM_021629.3
HARS NM_002109.5
HSPB1 NM_001540.3
HSPB8 NM_014365.2
INF2* NM_022489.3
LITAF NM_004862.3
LMNA NM_170707.3
LRSAM1 NM_138361.5
MARS NM_004990.3
MFN2 NM_014874.3
MORC2 NM_014941.2
MPZ NM_000530.6
NEFL NM_006158.4
PMP22 NM_000304.3
RAB7A NM_004637.5
TFG NM_006070.5
TRPV4 NM_021625.4
YARS NM_003680.3

INF2: Readthrough analysis is not offered for exon 8.