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P405 CMT1

SALSA® MLPA® Probemix P405 CMT1 detects deletions and duplications in the PMP22 gene, and deletions in the GJB1 gene.

Specifications

Contents: 42 MLPA probes, including 11 probes for the PMP22 gene (IVD, 3 upstream), an additional 4 probes for the common 17p12 deletion/duplication region (RUO), 7 probes for MPZ (RUO), 5 probes for GJB1 (IVD) and 3 probes for the X-chromosome (RUO).

Tissue: genomic DNA isolated from human peripheral whole blood

Application: Charcot-Marie-Tooth disease type 1A (CMT1A) (duplications in PMP22), X-linked CMT (CMT1X) (deletions in GJB1), and hereditary neuropathy with liability to pressure palsies (HNPP) (deletions in PMP22).

IVDR certified and registered for in vitro diagnostic (IVD) use in selected territories.

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List Prices Documentation

Key related products

P033 CMT1

Contains probes for the 17p12 chromosomal region and KIF1b gene.

P143 MFN2-MPZ

Contains probes for the MFN2 and MPZ genes.

P307 SEPT9

Contains probes for the SEPT9 gene involved in hereditary neuralgic amyotrophy.

View all

Intended purpose

The SALSA MLPA Probemix P405 CMT1 is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative manual assay for the detection of deletions or duplications in the human PMP22 gene and deletions in the GJB1 gene in genomic DNA isolated from human peripheral whole blood specimens. P405 CMT1 is intended to confirm a potential cause for Charcot-Marie-Tooth disease type 1A (CMT1A) (duplications in PMP22) and X-linked CMT (CMT1X) (deletions in GJB1) or confirm a potential cause for and clinical diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) (deletions in PMP22) and for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

Clinical background

Charcot-Marie-Tooth disease (CMT), with an average prevalence of 14.5 per 100 000, varying from 9.7 per 100 000 to 82.3 per 100 000, is the most common hereditary sensorimotor neuropathy, comprising a group of clinically and genetically heterogeneous peripheral neuropathies. CMT is characterized by progressive distal muscle atrophy and weakness, sensory disturbance, the absence of deep tendon reflexes, and pes cavus deformity of the foot. More than 80 different genes are associated with CMT (http://www.ncbi.nlm.nih.gov/books/NBK1358/). Subtypes related to the genes PMP22, GJB1, MPZ and MFN2 are the most common ones, being responsible for up to 95% of CMT cases with a final diagnosis (Padilha et al. 2020). The disease can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. Table 1 provides an overview of the different genes involved in the CMT subtypes and the probemixes that cover these genes.

The most frequent form, CMT1A, accounts for as much as 50% of all CMT cases. CMT1A is a dominantly inherited, childhood-onset, slowly progressive motor and sensory neuropathy due to a duplication of PMP22 on chromosome 17. CMT1B accounts for an additional ~10% of CMT1 patients. The gene involved in CMT1B is myelin protein zero (MPZ). CMT1A and 1B are clinically indistinguishable; classification is based solely on molecular findings.

X-linked CMT (CMTX) is characterized by moderate to severe motor and sensory neuropathy in affected males and usually mild to no symptoms in carrier females. Subtype CMT1X accounts for about 90% of X-linked CMT, and is caused by mutations in the gap-junction protein beta 1 (GJB1) gene (https://www.ncbi.nlm.nih.gov/books/NBK1374/).

Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by repeated focal pressure neuropathies such as carpal tunnel syndrome and peroneal palsy with foot drop. Recovery from acute neuropathy is often complete; when recovery is not complete, the resulting disability is usually mild. Some affected individuals also have signs of a mild to moderate peripheral neuropathy. The prevalence of HNPP is estimated at 1 per 50,000 to 1 per 20,000. The penetrance is 100% but expressivity is highly variable even within the same family. Approximately 6-23% of individuals diagnosed with HNPP have an asymptomatic affected parent. A contiguous gene deletion of chromosome 17p12 that includes PMP22 is present in approximately 80% of affected individuals; the remaining 20% have a pathogenic variant in PMP22 (https://www.ncbi.nlm.nih.gov/books/NBK1392/).

Table 1. Overview of the probemixes and genes related to CMT.

Probemix* Genes and coverage Condition Remarks
P033-B4 CMT1 (IVD)

PMP22: all exons

KIF1b: 2 probes

CMT1A and HNPP

CMT2A1

PMP22 probes in P033-B4 have the same ligation site as PMP22 probes in P405-B1 except for one exon 1 probe and one exon 4 probe. There is one additional PMP22 exon 5 probe present in P033-B4.
P405-B1 CMT1 (IVD)

PMP22: all exons

MPZ: all exons

GJB1: all exons

CMT1A and HNPP

CMT1B

CMTX

PMP22 probes in P405-B1 have the same ligation sites as PMP22 probes in P033-B4 except for one exon 1 probe and one exon 4 probe. There is one additional PMP22 exon 5 probe present in P033-B4.

MPZ probes in P405-B1 have the same ligation sites as MPZ probes in P143-C3.
P143-C3 MFN2-MPZ (RUO)

MFN2: all exons

MPZ: all exons

CMT2A

CMT1B

MPZ probes in P143-C3 have the same ligation sites as MPZ probes in P405-B1.

* IVD: in vitro diagnostic. RUO: research use only.

Several types and subtypes of Charcot-Marie-Tooth disease exist, each involving a different gene or locus. Furthermore, there is a large overlap in clinical phenotype between the different types of CMT. Other disorders with comparable clinical features have been described, including hereditary neuralgic amyotrophy (HNA), amyloid neuropathies, Krabbe disease and hereditary ataxias. Therefore, molecular diagnosis may be complicated for certain patients.

Regulatory status

SALSA MLPA Probemix P405 CMT1 is CE-marked under the IVDR for in vitro diagnostic (IVD) use in Europe. This assay has also been registered for IVD use in Colombia and Israel.

This assay is for research use only (RUO) in all other territories.

Product documentation

Version B1

Other versions

Contact us for earlier versions.

Translations and Summary of Safety and Performance

Translations of the product description in selected European languages are available upon request. Please contact us or one of our local sales partners. Translations of the MLPA General Protocol in selected languages are available here.

The Summary of Safety and Performance (SSP) is also available upon request.

List prices

Product

Item no.
Description
Technology
Price
P405-025R
SALSA MLPA Probemix P405 CMT1 – 25 rxn
MLPA
€ 286.00
P405-050R
SALSA MLPA Probemix P405 CMT1 – 50 rxn
MLPA
€ 560.00
P405-100R
SALSA MLPA Probemix P405 CMT1 – 100 rxn
MLPA
€ 1096.00

Required reagents

A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM (6 vials)
MLPA MS-MLPA
€ 348.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
MLPA MS-MLPA
€ 348.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 1600.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
MLPA MS-MLPA
€ 1600.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 6152.00

Price details & ordering

The prices above are list prices for direct orders from MRC Holland. Contact us for a quote that takes discounts and additional costs (such as shipping costs) into account. Different prices apply for orders through one of our sales partners; contact your local supplier for a quote.

More information about ordering & prices

Positive samples

Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.

The commercially available positive samples below have been tested with the current (B1) version of this product and have been shown to produce useful results.

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P405 CMT1

  • Ando M et al. (2022). Comprehensive Genetic Analyses of Inherited Peripheral Neuropathies in Japan: Making Early Diagnosis Possible. Biomedicines. 10:1546.
  • Brown SB et al. (2014). Point Mutation Analysis of PMP22 in Patients Referred for Hereditary Neuropathy with Liability to Pressure Palsies. Open J Genet. 4:426-33.
  • DiVincenzo C et al. (2014). The allelic spectrum of Charcot-Marie-Tooth disease in over 17,000 individuals with neuropathy. Mol Genet Genomic Med. 2:522-9.
  • Ferese R et al. (2021). Cohort Analysis of 67 Charcot-Marie-Tooth Italian Patients: Identification of New Mutations and Broadening of Phenotype Expression Produced by Rare Variants. Front Genet. 12:682050.
  • Gui B et al. (2016). A New Next-Generation Sequencing-Based Assay for Concurrent Preimplantation Genetic Diagnosis of Charcot-Marie-Tooth Disease Type 1A and Aneuploidy Screening. J Genet Genomics. 43:155-9.
  • Kulshrestha R et al. (2017). Deletion of P2 promoter of GJB1 gene a cause of Charcot-Marie-Tooth disease. Neuromuscul Disord. 27:766-70.
  • Milley GM et al. (2018). Genotypic and phenotypic spectrum of the most common causative genes of Charcot-Marie-Tooth disease in Hungarian patients. Neuromuscul Disord. 28:38-43.
  • Nagappa M et al. (2020). PMP22 Gene-Associated Neuropathies: Phenotypic Spectrum in a Cohort from India. J Mol Neurosci. 70:778-89.
  • Shahrizaila N et al. (2014). X-linked Charcot-Marie-Tooth disease predominates in a cohort of multiethnic Malaysian patients. Muscle Nerve. 49:198-201.
  • Wang R et al. (2015). Clinical and genetic spectra in a series of Chinese patients with Charcot-Marie-Tooth disease. Clin Chim Acta. 451:263-70.

References

  • Padilha JPD et al. (2020). Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies. Clin Genet. 98:185-90.
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Choose your country to see the products for your location

CE

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

CE2797

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

CO

IVD-registered in Colombia.

IL

IVD-registered in Israel.