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P189 CDKL5/ARX/FOXG1

SALSA® MLPA® Probemix P189 CDKL5/ARX/FOXG1 detects deletions in the CDKL5 gene, and deletions and duplications in the FOXG1 gene.

Specifications

Contents: 52 MLPA probes, including 24 probes for the CDKL5 region, 5 probes for ARX, 12 probes for NTNG1 and 2 probes for the FOXG1 region.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: CDKL5 deficiency disorder, and FOXG1 syndrome.

IVDR certified and registered for in vitro diagnostic (IVD) use in selected territories. Not all targets are for IVD use.

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List Prices Documentation

Key related products

P015 MECP2

Contains probes for the MECP2, CDKL5, ARX and NTNG1 genes.

P075 TCF4-FOXG1

Contains three additional probes for the FOXG1 gene. The ligation sites of the FOXG1 probes are identical to those in P395 MECF2-FOXG1, with the exception of one of the exon 1 probes.

P106 X-linked ID

Contains three probes for the ARX gene. The ligation sites of these probes are identical to probes included in P189 CDKL5/ARX/FOXG1.

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This product has recently been CE-marked for in vitro diagnostic (IVD) use under the In Vitro Diagnostic Regulation (IVDR; EU 2017/746), which replaces the former CE-marking under the IVD Directive (IVDD; Directive 98/79/EC). This update was accompanied by a change in the intended purpose and a change in format of the product description. Some information can now be found in a different location (more information).

Intended purpose

The SALSA MLPA Probemix P189 CDKL5/ARX/FOXG1 is an in vitro diagnostic (IVD) semi-quantitative manual assay for the detection of deletions in the CDKL5 gene, in order to confirm a potential cause for or clinical diagnosis of CDKL5 deficiency disorder. P189 CDKL5/ARX/FOXG1 can also be used for the detection of deletions or duplications in the FOXG1 gene, in order to confirm a potential cause for or clinical diagnosis of FOXG1 syndrome. This assay is intended for use with genomic DNA isolated from human peripheral whole blood specimens.

Certain probes targeting additional genes included in P189 CDKL5/ARX/FOXG1 may only be used in a research setting. The following table summarises which probes are for IVD, and which are exclusively restricted to RUO use.

IVD targets
RUO targets
CDKL5, FOXG1
NTNG1, ARX

For the full intended purpose, see the product description.

Clinical background

CDKL5 deficiency disorder (CDD) is a condition characterized by a broad range of clinical symptoms and severity. The primary symptoms include early-onset epilepsy (starting within the first three months of life), generalized hypotonia, psychomotor development disorders, intellectual disability, and cortical vision disorders. In addition to these primary symptoms, a number of accompanying symptoms have been reported, e.g. autistic features, poor eye contact, repetitive hand movements, vegetative disorders, gastrointestinal problems and distinctive facial features (GeneReviews). The prevalence of CDD is estimated at ~1:40,000-60,000 live births, with females affected four times more than men (Jakimiec et al. 2020). However, the course of disease is usually more severe in male patients.

CDD is also known as early infantile epileptic encephalopathy 2 (EIEE2) and was previously classified as an atypical form of Rett syndrome, i.e. the early-onset seizure variant of Rett syndrome. Rett syndrome and CDD have several common features, including seizures and intellectual disability, although only 23.7% of CDD patients meet clinical criteria for Rett syndrome (Olson et al. 2019). Other signs and symptoms of CDD are distinct from those of Rett syndrome, and CDD is now considered a separate clinical entity (Fehr et al. 2013).

FOXG1 syndrome is a condition characterized by impaired development and structural brain abnormalities. Affected infants are small at birth, and their heads grow at a reduced rate, leading to microcephaly by early childhood. The condition is associated with a particular pattern of brain malformations that includes a thin or underdeveloped corpus callosum, reduced gyri on the surface of the brain, and a reduced amount of white matter. FOXG1 syndrome affects most aspects of development, and children with the condition typically have severe intellectual disability. Abnormal or involuntary movements, such as jerking movements of the arms and legs and repeated hand motions, are common, and most affected children do not learn to sit or walk without assistance. Babies and young children with FOXG1 syndrome often have feeding problems, sleep disturbances, seizures, irritability, and excessive crying. Affected individuals may have autism spectrum disorder, which is characterized by limited communication and social interaction, including poor eye contact and a near absence of speech and language skills.

FOXG1 syndrome was previously described as a congenital variant of Rett syndrome. However, Rett syndrome is diagnosed almost exclusively in females, while FOXG1 syndrome affects both males and females. Because of these differences, physicians and researchers now usually consider FOXG1 syndrome to be distinct from Rett syndrome.

Condition Genes Probemix and coverage Remarks
Classic Rett syndrome

MECP2

(4 exons)

P015-F2: Each exon

 -
MECP2 duplication syndrome

MECP2

(4 exons)

P015-F2: Each exon

 -
Atypical Rett syndrome

MECP2

(4 exons)

P015-F2: Each exon

 -

NTNG1

(6 exons)

P189-C2: Each exon

P015-F2: Exons 2, 3, 5, 6

 Exon 3, 5 and 6 probes in P015 have the same ligation site as probes in P189.
CDKL5 deficiency disorder

CDKL5

(21 exons)

P189-C2: Each exon

P015-F2: Exons 3, 6, 9, 10

 Probes in P015 have the same ligation sites as probes in P189.
Early infantile epileptic encephalopathy 1

ARX

(5 exons)

P189-C2: Each exon

P015-F2: Exons 1, 5

 Probes in P015 have the same ligation sites as probes in P189.
FOXG1 syndrome

FOXG1

(1 exon)

P189-C2: Exon 1 and upstream region

 -

Regulatory status

SALSA MLPA Probemix P189 CDKL5/ARX/FOXG1 is CE-marked under the IVDR for in vitro diagnostic (IVD) use in Europe. This assay has also been registered for IVD use in Israel.

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

Product documentation

Version C2

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
P189-025R
SALSA MLPA Probemix P189 CDKL5/ARX/FOXG1 – 25 rxn
MLPA
€ 286.00
P189-050R
SALSA MLPA Probemix P189 CDKL5/ARX/FOXG1 – 50 rxn
MLPA
€ 560.00
P189-100R
SALSA MLPA Probemix P189 CDKL5/ARX/FOXG1 – 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 (C2) version of this product and have been shown to produce useful results.

CDKL5

  • Coriell NA23710 (f): Heterozygous deletion affecting the probes for CDKL5 intron 16-exon 18.

FOXG1

  • Coriell NA01750 (m): Heterozygous duplication affecting the probes for FOXG1.
  • Coriell NA22765 (m): Heterozygous deletion affecting the probes for FOXG1.

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P189 CDKL5/ARX/FOXG1

  • Bartnik M et al. (2011). Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females. Genet Med. 13:447-52.
  • Bartnik M et al. (2012). Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders. Am J Med Genet B Neuropsychiatr Genet. 159B:760-71.
  • Boutry-Kryza N et al. (2014). Complex mosaic CDKL5 deletion with two distinct mutant alleles in a 4-year-old girl. Am J Med Genet A. 164A:2025-8.
  • Jähn J et al. (2013). CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients. J Child Neurol. 28:937-41.
  • Maortua H et al. (2012). CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain. BMC Med Genet. 13:68.
  • Mei D et al. (2010). Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy. Epilepsia. 51:647-54.
  • Mei D et al. (2014). Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys. Epilepsia. 55:1748-53.
  • Nemos C et al. (2009). Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature. Clin Genet. 76:357-71.
  • Specchio N et al. (2023). CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome. Cereb Cortex. 33:9709-17.
  • Trump N et al. (2016). Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis. J Med Genet. 53:310-7.

References

  • Fehr S et al. (2013). The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy. Eur J Hum Genet. 21:266-73.
  • Jakimiec M et al. (2020). CDKL5 Deficiency Disorder-A Complex Epileptic Encephalopathy. Brain Sci. 10:107.
  • Olson HE et al. (2019). Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review. Pediatr Neurol. 97:18-25.
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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.

IL

IVD-registered in Israel.