General information
The SALSA MLPA Probemix P071 LMNB1-PLP1-NOTCH3 is a research use only (RUO) assay for the detection of deletions or duplications in the LMNB1, PLP1 and NOTCH3 genes, which are associated with autosomal dominant leukodystrophy with autonomic disease (ADLD), Pelizaeus-Merzbacher disease (PMD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively.

Autosomal dominant leukodystrophy with autonomic disease (ADLD) is a slowly progressive neurological disorder that is characterized by widespread loss of myelin in the central nervous system. Symptoms develop in the fourth or fifth decade of life and include problems with the autonomous nervous system, followed by movement difficulties. ADLD is caused by mutations in the LMNB1 gene on chromosome 5q23.2, with most cases resulting from a duplication of the LMNB1 gene.

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked neurological disorder that is caused by demyelination in the central nervous system. The age of onset is typically during infancy or early childhood. PMD is caused by mutations in the PLP1 gene on chromosome Xq22.2. Duplication of the complete PLP1 gene accounts for 50-70% of PMD cases, whereas point mutations and deletions are involved in the majority of the remaining cases. In addition to PMD, defects in the PLP1 gene can also result in spastic paraplegia type 2 (SPG2).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition characterized by migraine, strokes, mood disorders, and cognitive decline that can result in dementia. CADASIL has a mid-adult onset and is caused by mutations in the NOTCH3 gene on chromosome 19p13.12. Defects in the NOTCH3 gene can also lead to lateral meningocele syndrome.

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 P071-B2 LMNB1-PLP1-NOTCH3 contains 34 MLPA probes with amplification products between 122 and 415 nucleotides. This includes 12 probes for the LMNB1 gene, one probe for each exon and two probes for exon 1. It also includes seven probes for the PLP1 gene, one probe for each exon with the exception of exon 1, and three probes for the NOTCH3 gene, targeting exons 2, 7 and 28. Three flanking probes are included that target regions centromeric and telomeric of the PLP1 gene. In addition, nine 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.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.