General information: The SALSA MLPA
Probemix P397 SCN4A-CACNA1S is a
research use only (RUO) assay for the detection of deletions or duplications in the
CACNA1S and
SCN4A genes, which are associated with hypokalemic periodic paralysis.
The nondystrophic myotonias and primary periodic paralyses are an important group of genetic muscle diseases characterised by dysfunction of ion channels that regulate membrane excitability. Clinical manifestations vary and include myotonia, hyperkalemic, hypokalemic periodic paralysis, progressive myopathy, and cardiac arrhythmias.
Hypokalemic periodic paralysis (HypokalemicPP) is most commonly associated with mutations in
CACNA1S gene (type 1 HypokalemicPP), which encodes the α subunit of the voltage-gated calcium channel, Cav1.1 (also known as the skeletal muscle L-type calcium channel, and the dihydropyridine receptor). Cav1.1 in the T-tubular membrane is attached to the ryanodine receptor of the sarcoplasmic reticulum, for which it acts as a voltage sensor. About 10% of hypokalemic periodic paralysis is associated with mutations in
SCN4A gene (type 2 HypokalemicPP), which encodes the skeletal muscle sodium channel.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1338/.
Probemix content: The SALSA MLPA Probemix P397-A3 SCN4A-CACNA1S contains 43 MLPA probes with amplification products between 131 and 490 nucleotides (nt). This includes 13 probes for the
CACNA1S gene, targeting 13 out of 44 exons of the gene, and 19 probes for the
SCN4A gene, targeting 19 out of 24 exons of the gene. In addition, eleven 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.