Intended use: The SALSA MLPA probemix P124 TSC1 is an in vitro diagnostic (IVD)
1 or a research use only (RUO) assay for the detection of deletions or duplications in the human
TSC1 gene, in order to confirm a potential cause and clinical diagnosis for tuberous sclerosis complex (TSC). This product can also be used for molecular genetic testing of at-risk family members. This assay is for use with human DNA extracted from peripheral blood and not for use with genomic DNA extracted from formalin-fixed paraffin embedded or fresh tumour material.
Deletions or duplications detected with the P124 TSC1 probemix must be confirmed by using another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in the
TSC1 gene are point mutations, none of which will be detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis of the
TSC1 gene. This assay is not intended to be used as a standalone assay for clinical decisions. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.
1Please note that this probemix is for In Vitro Diagnostic use (IVD) in the countries specified at the end of this product description. In all other countries, the product is for Research Use Only (RUO).
Clinical background: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by seizures and intellectual disability/developmental delay, and by abnormalities of the skin, brain, kidney, heart, and lungs. Central nervous system tumours are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death. The diagnosis of TSC is based on clinical findings and affects approximately 1 in 6000 live births. TSC is inherited in an autosomal dominant manner and is caused by mutations in either the
TSC1 or
TSC2 gene.
TSC2 mutations account for the majority (51%-82%) of all TSC patients as compared to
TSC1 mutations (~24%) (Sancak et al. 2005).
TSC2 mutations appear to be more common in sporadic TSC cases, while inherited cases result from
TSC1 and
TSC2 mutations in a nearly equal proportion. Presently, more than 450 different disease-causing mutations are known for
TSC1 and more than 1300 are known for
TSC2. Truncating mutations are the most common mutation type in the
TSC1 (80%) and the
TSC2 (65%) genes. Large genomic deletions are rare in
TSC1 (3%), but occur more frequently in the
TSC2 gene (6%) (Mayer et al. 2014). The frequency of somatic mosaicism for large deletions and duplications in the
TSC1 and
TSC2 genes in affected individuals with TSC has been reported as ~5% (Kozlowski et al. 2007).
More information is available on
https://www.ncbi.nlm.nih.gov/books/NBK1220/.
Probemix content: The P124-C3 probemix contains 32 probes with amplification products between 138 and 445 nt. This probemix contains one probe for each exon of the
TSC1 gene. In addition, 9 reference probes are included in the P124-C3
TSC1 probemix, detecting several different autosomal chromosomal locations. The identity of the genes detected by the reference probes is available online (
www.mlpa.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity Fragments (Q-fragments), two DNA Denaturation Fragments (D-fragments), one benchmark fragment, one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at
www.mlpa.com.