The SALSA MLPA probemixes P041 ATM-1 and P042 ATM-2 are in vitro diagnostic (IVD)1
or research use only (RUO) assays for the detection of deletions or duplications in the human ATM
gene in order to confirm a potential cause and clinical diagnosis for Ataxia-Telangiectasia or hereditary predisposition to develop cancer, including but not limited to breast cancer. 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 DNA extracted from formalin-fixed paraffin embedded or fresh tumour materials. Deletions or duplications detected with the P041/P042 probemixes must be verified by another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in ATM
are point mutations, none of which will be detected by MLPA. It is therefore recommended to use these SALSA MLPA probemixes in combination with sequence analysis of the ATM
This assay is not intended to be used as a standalone assay for clinical decisions. The results of this test must be interpreted by a molecular geneticist or equivalent.
Please 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).
Mutations in the ATM
gene cause Ataxia-Telangiectasia (A-T, also known as Louis-Bar syndrome). A-T is an autosomal recessive disorder affecting the nervous system, immune system and several other organs. It is characterised by progressive cerebellar ataxia, telangiectases, and a predisposition to malignancy, particularly leukaemia and lymphoma. A-T patients often have a weakened immune system and develop chronic lung infections. It occurs in 1 in 40,000 to 100,000 people worldwide.
The ATM protein is a member of the phosphatidylinositol-3 kinase family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. This could explain the increased risk in ATM-heterozygotes of developing malignancies, in particular breast cancer. Around 1% of breast cancer patients harbour mutations in ATM
(Buys et al. 2017, Lerner-Ellis et al. 2015). The relative risk for developing breast cancer is estimated to be two to four fold compared to the general population (Tavtigian et al. 2009, Thompson et al. 2005). Germline heterozygous pathogenic ATM
variants have also been reported in several types of leukaemia and lymphoma and hereditary pancreatic cancer (Bullrich et al. 1999, Oguchi et al. 2003, Roberts et al. 2012).
The P041-B1 and the P042-B2 probemixes each contain 34 probes for the ATM
gene. When used together, a probe for each ATM
exon is present, including one probe for intron 1, two probes for exon 1 and 61 and two probes for intron 61.
The P041-B1 probemix contains 45 MLPA probes with amplification products between 130 and 485 nt in length including 11 reference probes. The P042-B2 probemix contains 45 probes with amplification products between 131 and 485 nt in length, 11 of which are reference probes. The identity of the genes detected by the reference probes is available online (www.mrcholland.com
These probemixes contain 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