General information: The SALSA MLPA Probemix P211 HSP region is a research use only (RUO) assay for the detection of deletions or duplications in the SPAST gene and other genes located in the 2p22.3 region and 15q11.2 region, which are associated with Hereditary spastic paraplegias (HSPs).
HSPs are a large and diverse group of genetically heterogeneous neurodegenerative disorders characterised by progressive lower limb/lower extremity spasticity and weakness. Defects in the SPAST gene (also known as SPG4) on chromosome 2p22 are identified as one of the causes for autosomal dominant pure HSP. The protein encoded by this gene is spastin which is involved in membrane shaping and modelling events.
This probemix contains probes for the first exon and intron and probes for exon 16 and 17 of the SPAST gene and the flanking regions of SPAST (2p22.3 region). This probemix furthermore contains probes for the NIPA1 gene (also known as SPG6) and probes for the nearby genes of NIPA1, such as the WHAMML1 and HERC2P2 genes (15q11.2 region). Probes for these flanking genes of NIPA1 have been included to distinguish NIPA1 defects from larger deletions in the Prader-Willi/Angelman syndrome region. The database of genomic variants mentions several copy number changes in this genomic region that have been found in healthy individuals (see http://dgv.tcag.ca/dgv/app/home).
Probemix content: The SALSA MLPA Probemix P211-B5 HSP region contains 39 MLPA probes with amplification products between 128 and 462 nucleotides (nt). This includes 13 probes for the 2p22.3 region, including probes for the SPAST gene. This probemix furthermore contains 13 probes for the 15q11.2 region, which encompasses the NIPA1, NIPA2, WHAMML1, and HERC2P2 genes. In addition, 13 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, 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.