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P226 SDH

SALSA® MLPA® Probemix P226 SDH detects copy number variations in the SDHB, SDHC, SDHD, SDHAF1 and SDHAF2 genes.

Specifications

Contents: 45 MLPA probes, including 9 probes for SDHB, 10 probes for SDHC, 7 probes for SDHD, 2 probes for SDHAF1 and 4 probes for SDHAF2.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: hereditary paraganglioma/pheochromocytoma (PGL/PCC).

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

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List Prices Documentation

Key related products

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Intended purpose

The SALSA MLPA Probemix P226 SDH is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative assay for the detection of deletions or duplications in SDHB, SDHC, SDHD, SDHAF1, and SDHAF2 in genomic DNA isolated from human peripheral whole blood specimens. P226 SDH is intended to confirm a potential cause for and clinical diagnosis of Hereditary Paraganglioma/Pheochromocytoma (PGL/PCC) and for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

Clinical background

Paragangliomas (PGLs) are neuroendocrine tumours that originate from neural crest-derived cells. They arise from sympathetic or parasympathetic paraganglia tissues and can be situated in the head and neck region, thorax, abdomen, and pelvis. Tumours that arise from the adrenal medulla are called pheochromocytomas (PCCs). Symptoms of PGL/PCC result either from mass effects (for example carotid body enlargement, visible in the neck) or catecholamine hypersecretion. PGLs are rare (incidence of ca. 2 in 1.000.000 individuals), and are most frequently found in individuals between the age of 30 and 50 years. For PCCs, the true incidence is unknown, as many affected individuals remain undiagnosed.

The hereditary PGL/PCC syndromes are inherited in an autosomal dominant manner. Pathogenic variants in the succinate dehydrogenase (SDH) genes, including SDHA, SDHB, SDHC, SDHD, and SDHAF2 (collectively referred to as SDHx) cause PGL/PCC and occur in up to 40% of cases. Probes for SDHA are not included in this P226 SDH probemix, but SALSA MLPA Probemix P429 SDHA-MAX-TMEM127 can be used to detect CNVs in the SDHA gene. SDHx genes are tumour suppressor genes and loss of heterozygosity is a second hit in tumours. SDHD and SDHAF2 demonstrate parent-of-origin effects and generally cause disease only when the pathogenic variant is inherited from the father (Hao et al. 2009, Hensen et al. 2004), with a penetrance of 90% or higher by the age of 70. Mutations in SDHA, SDHB and SDHC are inherited in an autosomal dominant manner with no parent-of-origin effect and show a low penetrance (Benn et al. 2006). Mutations in the SDHAF1 gene are a cause of the recessive disorder SDH defective infantile leukoencephalopathy (Ghezzi D et al. 2009), SDHAF1 loss-of-function might also cause PGL due to the function of SDHAF1 in the SDH complex. This association, however, has not yet been established.

It is estimated that 10-25% of hereditary PGL/PCC syndrome cases are caused by pathogenic variants in the SDHB gene, 2-8% in the SDHC gene, 8-9% in the SDHD gene. SDHAF2 mutations are very rare (<0.1%). The majority of mutations in the SDHx genes are point mutations and small deletions. It is estimated that 1.2-5.5% of patients with hereditary PGL/PCC have pathogenic CNVs in SDHB, SDHC, or SDHD, which include the known founder mutations: SDHB Dutch founder deletion in exon 3 and the SDHB Spanish founder deletion in exon 1 (Bayley et al. 2005, 2009, Buffet et al. 2012), all of which can be detected with this probemix.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1548/.

Regulatory status

SALSA MLPA Probemix P226 SDH is CE-marked under the IVDD 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 D1

Other versions

Contact us for earlier versions.

List prices

Product

Item no.
Description
Technology
Price
P226-025R
SALSA MLPA Probemix P226 SDH – 25 rxn
MLPA
€ 286.00
P226-050R
SALSA MLPA Probemix P226 SDH – 50 rxn
MLPA
€ 560.00
P226-100R
SALSA MLPA Probemix P226 SDH – 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 (D1) version of this product and have been shown to produce useful results.

SDHC

SDHAF2

  • Coriell NA20775: Heterozygous duplication affecting the probes for SDHAF2 exon 2-4.

SDHD

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P226 SDH

  • Andrews KA et al. (2018). Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. J Med Genet. 55:384-94.
  • Bernardo-Castiñeira C et al. (2019). Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations. J Clin Endocrinol Metab. 104:5673-92.
  • De Vos B et al. (2018). A novel succinate dehydrogenase subunit B germline variant associated with head and neck paraganglioma in a Dutch kindred: A family-based study. Clin Otolaryngol. 43:841-5.
  • Donato S et al. (2019). SDHx-related pheochromocytoma/paraganglioma - genetic, clinical, and treatment outcomes in a series of 30 patients from a single center. Endocrine. 65:408-15.
  • Hensen EF et al. (2011). Mutations in SDHD are the major determinants of the clinical characteristics of Dutch head and neck paraganglioma patients. Clin Endocrinol (Oxf). 75:650-5.
  • Hensen EF et al. (2012). High prevalence of founder mutations of the succinate dehydrogenase genes in the Netherlands. Clin Genet. 81:284-8.
  • Niemeijer ND et al. (2017). The phenotype of SDHB germline mutation carriers: a nationwide study. Eur J Endocrinol. 177:115-25.
  • Richter S et al. (2022). Head/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine. Endocr Relat Cancer. 29:213-24.
  • Rijken JA et al. (2019). Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers. Cancers (Basel). 11:103.
  • Yonamine M et al. (2021). Prevalence of Germline Variants in a Large Cohort of Japanese Patients with Pheochromocytoma and/or Paraganglioma. Cancers (Basel). 13:4014.

References

  • Bayley JP et al. (2005). The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet. 6:39.
  • Bayley JP et al. (2009). The first Dutch SDHB founder deletion in paraganglioma-pheochromocytoma patients. BMC Med Genet. 10:34.
  • Benn DE et al. (2006). Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab. 91:827-36.
  • Buffet A et al. (2012). A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma. Horm Metab Res. 44:359-66.
  • Ghezzi D et al. (2009). SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Nat Genet. 41:654-6.
  • Hao HX et al. (2009). SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science. 325:1139-42.
  • Hensen EF et al. (2004). Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families. Oncogene. 23:4076-83.
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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.

CO

IVD-registered in Colombia.

IL

IVD-registered in Israel.