The SALSA MLPA Probemix P046 TSC2 is an in vitro diagnostic (IVD)1
or research use only (RUO) semi-quantitative assay2
for the detection of deletions or duplications in the TSC2
gene in genomic DNA isolated from human peripheral whole blood specimens. P046 TSC2 is intended to confirm a potential cause for and clinical diagnosis of tuberous sclerosis complex (TSC) and for molecular genetic testing of at-risk family members.
Copy number variations (CNVs) detected with P046 TSC2 should be confirmed by using SALSA MLPA probemix P337 TSC2 Confirmation assay or with a different technique. In particular, CNVs detected by only a single probe always require confirmation by another method. Most defects in the TSC2
gene are point mutations, none of which will be detected by MLPA. It is therefore recommended to use this assay in combination with sequence analysis.
Assay results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, parental evaluation, clinical genetic evaluation, and counselling, as appropriate. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.
This device is not intended to be used for standalone diagnostic purposes, pre-implantation or prenatal testing, population screening, or for the detection of, or screening for, acquired or somatic genetic aberrations, e.g. from DNA extracted from formalin-fixed paraffin embedded (FFPE) or fresh tumour materials.
Please note that this probemix is for in vitro diagnostic (IVD) use in the countries specified at the end of the product description. In all other countries, the product is for research use only (RUO).
To be used in combination with a SALSA MLPA Reagent Kit and Coffalyser.Net analysis software.
Tuberous sclerosis complex (TSC) is a genetic disorder characterised 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 worldwide. Prevalence is estimated to be 1 in 11.300-25.000 in Europe. TSC is inherited in an autosomal dominant manner and is caused by mutations in either the TSC1
mutations account for the majority (~69%) of all TSC patients as compared to TSC1
mutations (~26%). TSC2
mutations appear to be more common in sporadic TSC cases, while inherited cases result from TSC1
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 (5%). The frequency of somatic mosaicism for large deletions and duplications in the TSC1
genes in affected individuals with TSC has been reported as ~5% (Kozlowski et al. 2007) up to 10-25% (Jang et al. 2012). Cases of mosaic partial TSC2
gene deletions have been reported (Sampson et al. 1997; Verhoef et al. 1999).
Some affected individuals have features of both TSC, caused by deletion of TSC2
and autosomal dominant polycystic kidney disease (ADPKD), caused by deletion of PKD1
. Individuals with the TSC2/PKD1 contiguous gene deletion syndrome are also at risk of developing the complications of ADPKD, which include cystic lesions in other organs (e.g., the liver).
More information is available on https://www.ncbi.nlm.nih.gov/books/NBK1220/
The SALSA MLPA Probemix P046-D1 TSC2 contains 52 MLPA probes with amplification products between 130 and 500 nucleotides (nt). This includes 42 probes for TSC2
and one flanking probe. In addition, nine reference probes are included that detect autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (www.mrcholland.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, and 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.mrcholland.com