General information
The SALSA MLPA Probemix P022 PLP1 is a research use only (RUO) assay for the detection of deletions or duplications in the PLP1 gene and the Xq22 region, which are associated with PLP1 disorders ranging from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia type 2 (SPG2).

PLP1 disorders are rare X-linked neurological disorders caused by pathogenic variants in the PLP1 gene and resulting in defective central nervous system myelination. The PLP1 gene encodes a transmembrane proteolipid protein that is the predominant component of myelin in the central nervous system. It may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. PMD (OMIM #312080) and SPG2 (OMIM #312920) are at opposite ends of the clinical spectrum of PLP1 disorders, PMD being more severe than SPG2. PMD symptoms can begin in infancy and include amongst others nystagmus, cognitive impairment, progressive spasticity, ataxia and hypotonia, with a shortened lifespan. SPG2 manifests as spastic paraparesis, usually with a normal life span.

The PLP1 gene (8 exons) spans ~16 kb of genomic DNA and is located on chromosome Xq22.2, about 103 Mb from the p-telomere. Complete duplication of the PLP1 gene can be found in up to up to 70% of the PMD cases, whereas deletions of this gene as well as point mutations in coding or splice site regions are involved in the majority of the remaining cases. Heterozygous females with a PLP1 duplication are usually asymptomatic.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1182/.

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.

Probemix content
The SALSA MLPA Probemix P022-B2 PLP1 contains 37 MLPA probes with amplification products between 142 and 445 nucleotides (nt). This includes seven probes for the PLP1 gene, one probe for each exon of the gene with the exception of exon 1, and 20 probes for the Xq22 region. In addition, ten reference probes are included that detect locations on the X-chromosome. Complete probe sequences and the identity of the genes detected by the reference probes are available 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.