The SALSA MLPA
Probemix P429 SDHA-MAX is a research use only (RUO)
assay for the detection of deletions or duplications in the SDHA
genes which are associated with pheochromocytomas (PCCs) and paragangliomas (PGLs).
PCCs and PGLs are genetically heterogeneous neural crest-derived neoplasms. Both are characterised by the growth of benign tumours in structures called paraganglia, affecting approximately one in four million people. Despite their benign character, these tumours can be associated with high morbidity and mortality due to mass effect, high amounts of circulating catecholamines and metastasis. Up to 40% of the PCC and PCL patients carry a germline mutation in 10 genes, among them are the MAX
gene (Albattal et al. 2019).
Mutations in the succinate dehydrogenase (SDH) complex subunit gene SDHA
, at 5p13.33, can lead to PCC and PGL with variable penetrance (Burchinon et al. 2010). Moreover, bi-allelic SDHA
mutations have been shown to cause an early onset neurodegenerative disorder known as Leigh syndrome (Hovarth et al. 2006).
Germline mutations in myc-associated factor X (MAX
), at 14q23.2, have been shown to be responsible for ~1% of PCC/PGL patients (Comino-Mendez et al. 2011; Burnichon et al. 2012). MAX
is a member of basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. Through its ability to form homo- or heterodimers with other family members, like MYC
is suggested to act as a tumour suppressor gene and to play an important role in cell proliferation, differentiation and apoptosis (for review see Deng 2012; Cascon and Robledo 2012). Recently, both germline and somatic intragenic copy number alterations of MAX
gene have been described (Korpershoek et al. 2016 and Daly et al. 2018).
This SALSA MLPA Probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.
The SALSA MLPA Probemix P429-B2 SDHA-MAX contains 42 MLPA probes with amplification products between 129 and 463 nucleotides (nt). This includes 10 probes for the SDHA
gene and 8 probes for the MAX
gene. This probemix also contains four flanking probes for the SDHA
and five flanking probes for the MAX
genes. In addition, 15 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.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, 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.mlpa.com