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SALSA MLPA Probemix P066 Marfan Syndrome-2

SALSA® MLPA® probemixes P065 Marfan Syndrome-1 and P066 Marfan Syndrome-2 detect copy number variations in the FBN1 and TFGBR2 genes.

Specifications

Contents: P065 and P066 together contain 101 MLPA probes, including 70 probes for FBN1 and 9 probes are for TGFBR2, covering all exons of both genes with at least one probe.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: Marfan syndrome (MFS) and other FBN1- and/or TGFBR2-related disorders.

CE-marked and registered for in vitro diagnostic (IVD) use in selected territories.

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List Prices Documentation

Key related products

SALSA MLPA Probemix P065 Marfan Syndrome-1

Marfan syndrome; other FBN1-related disorders; other TGFBR2-related disorders. Contains probes for all FBN1 exons when used together with P066 and contains probes for TGFBR2.

SALSA MLPA Probemix P148 TGFBR1-TGFBR2

Contains probes for TGFBR1 and TGFBR2, involved in aortic aneurysm syndrome. The majority of the TGFBR2 probes in P148 have the same ligation site as the TGFBR2 probes in P065.

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Intended purpose

The SALSA MLPA Probemixes P065 Marfan Syndrome-1 and P066 Marfan Syndrome-2 are in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative assays for the detection of deletions or duplications in the FBN1 gene, in order to confirm a potential cause for and clinical diagnosis of Marfan syndrome and other FBN1-related disorders. P065 Marfan Syndrome-1 can also be used for the detection of deletions or duplications in the TGFBR2 gene, in order to confirm a potential cause for and clinical diagnosis of TGFBR2-related disorders. Both assays are for use with genomic DNA isolated from human peripheral whole blood specimens and are also intended for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

Clinical background

Marfan syndrome is a systemic disorder of connective tissue that mainly affects the ocular, skeletal and cardiovascular systems. It has a penetrance of 100%, but a high degree of clinical variability, with phenotypes ranging from isolated features of Marfan syndrome to neonatal presentation of severe and progressive disease in multiple organ systems. The major causes of morbidity and mortality relate to the cardiovascular system. However, if proper management is executed, the life expectancy of a patient with Marfan syndrome approximates that of the general population. Marfan syndrome is an autosomal dominant disease with a prevalence of 1:5,000 – 1:10,000 that is caused by mutations in the FBN1 gene (Dietz et al. 1991; Lee et al. 1991). In ~90-93% of patients diagnosed with Marfan syndrome a mutation is detected by sequencing of the FBN1 coding region and flanking intronic regions. In ~5% of the patients, the pathogenic variant identified is a large deletion or duplication (Baetens et al. 2011; Hilhorst-Hofstee et al. 2011; Mannucci et al. 2020; Rand-Hendriksen et al. 2007; Stengl et al. 2020). In a small percentage of patients (~2-5%), no mutation in FBN1 is identified. More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1335/.

Several Marfan-related disorders have been recognized that display a specific subset of the phenotypic features found in Marfan syndrome and that can also be caused by mutations in the FBN1 gene. These FBN1-related disorders include MASS phenotype (mitral valve, aortic, skin and skeletal features), ectopia lentis syndrome and familial thoracic aortic aneurysm and dissection (familial TAAD). In addition, there are also Marfan-related disorders that are caused by mutations in TGFBR2. These TGFBR2-related disorders include Loeys-Dietz syndrome and familial TAAD. Loeys-Dietz syndrome is a systemic disorder of connective tissue that has a large overlap in clinical features with Marfan syndrome. The most common clinical features involve the vascular, skeletal, craniofacial, cutaneous, allergic/inflammatory and ocular systems. In ~55-60% of patients diagnosed with Loeys-Dietz syndrome a pathogenic variant in TGFBR2 is identified. Sequence analysis detects ~100% of these pathogenic variants. Large rearrangements of TGFBR2 have thus far not been reported in patients with Loeys-Dietz syndrome features. There is one report of a deletion encompassing the entire TGFBR2 gene, but this individual thus far lacked aortic involvement and did not show clear features of Loeys-Dietz syndrome (Campbell et al. 2011). More information about Loeys-Dietz syndrome is available at https://www.ncbi.nlm.nih.gov/books/NBK1133/.

Regulatory status

SALSA MLPA Probemix P066 Marfan Syndrome-2 is CE-marked for in vitro diagnostic (IVD) use. 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 C1

Other versions

Contact us for earlier versions.

List prices

Product

Item no.
Description
Technology
Price
P066-025R
SALSA MLPA Probemix P066 Marfan Syndrome-2 – 25 rxn
MLPA
€ 281.00
P066-050R
SALSA MLPA Probemix P066 Marfan Syndrome-2 – 50 rxn
MLPA
€ 550.00
P066-100R
SALSA MLPA Probemix P066 Marfan Syndrome-2 – 100 rxn
MLPA
€ 1075.00

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
€ 341.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
MLPA MS-MLPA
€ 341.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 1571.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
MLPA MS-MLPA
€ 1571.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 6037.00

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 (C1) version of this product and have been shown to produce useful results.

  • Coriell NA03184: Heterozygous duplication affecting the probes for FBN1.
  • Coriell NA21939: Heterozygous deletion affecting the probes for FBN1 exon 43-44.
  • Coriell NA21940: Heterozygous deletion affecting the probes for FBN1 exon 45-47.

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P066 Marfan Syndrome-2

  • Buki G et al. (2023). Correlation between large FBN1 deletions and severe cardiovascular phenotype in Marfan syndrome: Analysis of two novel cases and analytical review of the literature. Mol Genet Genomic Med. 11:e2166.
  • Chen ZX et al. (2023). Genotype Impacts Axial Length Growth in Pseudophakic Eyes of Marfan Syndrome. Invest Ophthalmol Vis Sci. 64:28.
  • Franken R et al. (2016). Genotype impacts survival in Marfan syndrome. Eur Heart J. 37:3285-90.
  • Franken R et al. (2017). Relationship between fibrillin-1 genotype and severity of cardiovascular involvement in Marfan syndrome. Heart. 103:1795-9.
  • Mannucci L et al. (2020). Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome: A 10-year single center experience. Clin Chim Acta. 501:154-64.
  • Mátyás G et al. (2007). Large genomic fibrillin-1 (FBN1) gene deletions provide evidence for true haploinsufficiency in Marfan syndrome. Hum Genet. 122:23-32.
  • Nayak SS et al. (2021). Clinically relevant variants in a large cohort of Indian patients with Marfan syndrome and related disorders identified by next-generation sequencing. Sci Rep. 11:764.
  • Pees C et al. (2014). Detection of 15 novel mutations in 52 children from 40 families with the Marfan or Loeys-Dietz syndrome and phenotype-genotype correlations. Clin Genet. 86:552-7.
  • Proost D et al. (2015). Performant Mutation Identification Using Targeted Next-Generation Sequencing of 14 Thoracic Aortic Aneurysm Genes. Hum Mutat. 36:808-14.
  • Yang H et al. (2018). Identification of gross deletions in FBN1 gene by MLPA. Hum Genomics. 12:46.

References

  • Baetens M et al. (2011). Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes. Hum Mutat. 32:1053-62.
  • Campbell IM et al. (2011). TGFBR2 deletion in a 20-month-old female with developmental delay and microcephaly. Am J Med Genet A. 155A:1442-7.
  • Dietz HC et al. (1991). Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 352:337-9.
  • Hilhorst-Hofstee Y et al. (2011). The clinical spectrum of complete FBN1 allele deletions. Eur J Hum Genet. 19:247-52.
  • Lee B et al. (1991). Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 352:330-4.
  • Mannucci L et al. (2020). Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome: A 10-year single center experience. Clin Chim Acta. 501:154-64.
  • Rand-Hendriksen S et al. (2007). Search for correlations between FBN1 genotype and complete Ghent phenotype in 44 unrelated Norwegian patients with Marfan syndrome. Am J Med Genet A. 143A:1968-77.
  • Stengl R et al. (2020). Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement. Orphanet J Rare Dis. 15:290.
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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.

IL

IVD-registered in Israel.