The SALSA MLPA
Probemix P481 PRKAR1A-ARMC5 is a research use only (RUO)
assay for the detection of deletions or duplications in the PRKAR1A
genes, which are associated with adrenal hyperplasia. PRKAR1A
is also associated with Carney complex.
is located on 17q24.2. It encodes a regulatory subunit of the cAMP-dependent protein kinase A (PKA) complex. This subunit inactivates PKA by binding to its catalytic subunits; cAMP causes dissociation of PRKAR1A from the catalytic subunits of PKA, activating them. Phosphorylation mediated by the cAMP/PKA signalling pathway is involved in the regulation of a wide variety of cellular processes. These include metabolism, cell proliferation, differentiation, and apoptosis.
Loss of function mutations in PRKAR1A
cause Carney complex (CNC, OMIM 160980), an autosomal dominant syndrome characterized by the onset of multiple types of neoplasia. These include endocrine, cardiac, and cutaneous tumours. Adrenocortical tumours in Carney complex often take the form of multiple small cortical pigmented nodules, similar to those in Cushing syndrome. Additionally, translocations resulting in fusion transcripts of PRKAR1A
have been observed in papillary thyroid carcinoma and acute promyelocytic leukaemia (Romei and Elisei 2012).
, located on 16p11.2,
is a member of the ARM (armadillo/beta-catenin-like repeat) superfamily, which has been implicated in mediating protein-protein interactions. The ARMC5 protein plays a role in adrenal gland growth homeostasis and corticosteroid synthesis.
Mutations in ARMC5
are associated with macronodular adrenal hyperplasia (OMIM 615954), an autosomal dominant susceptibility to tumours of the adrenal glands. This often results in clinical Cushing syndrome (Assié et al. 2013). The susceptibility to adrenal tumours has incomplete penetrance, as a somatic second hit to the ARMC5
gene is required for tumour development.
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 P481-A1 PRKAR1A-ARMC5 contains 49 MLPA probes with amplification products between 130 and 481 nucleotides (nt). This includes 14 probes for PRKAR1A
, eight probes for ARMC5,
and 14 probes in the flanking regions of the PRKAR1A
genes. In addition, 13 reference probes are included that target relatively copy number stable regions in various cancer types including adrenal tumours. Probe sequences and the identity of the genes detected by the flanking and reference probes are available in Tables 2 and 3 and 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