General information
SALSA^® MLPA^® Probemix P369 Smith-Magenis is a research use only (RUO) assay for detection of deletions or duplications in the 17p11.2 chromosomal region. Deletion of this region is associated with Smith-Magenis syndrome (SMS), whereas duplication of this region is associated with Potocki-Lupski syndrome (PTLS). SMS is a developmental disorder characterised by craniofacial anomalies, and several neurological and behavioural abnormalities. It is primarily caused by an interstitial deletion on chromosome 17p11.2 where the gene RAI1, included in this probemix, is located. In most cases (~70%), SMS is due to a ~3.7 Mb deletion, but atypical (smaller or larger) deletions, as well as RAI1 mutations have also been found in patients (Elsea & Girirajan 2008).

Haploinsufficiency of RAI1 is therefore thought to play a major role in the SMS phenotype (Elsea & Girirajan 2008). Other genes located in the 17p11.2 critical region that have also been implicated to play a role in some SMS features, namely MY015A (deafness), TNFRSF13B (immune deficiency), PEMT (fatty liver), and ALDH3A2 (dry skin), as well as PMP22 (neuropathy development) which is flanking this region, are also covered (Vilboux et al. 2011 and Poisson et al. 2019).

Furthermore, five probes targeting the 2q37.3 region are included, among which probes targeting the HDAC4 gene. Haploinsufficiency (either by a mutation or deletion) of the HDAC4 gene causes chromosome 2q37 deletion syndrome, which has an overlapping phenotype with SMS. Furthermore, deletion or mutation of the HDAC4 gene results in reduced expression of RAI1 (Williams et al. 2010, Trang et al. 2019).

Duplication of the same ~3.7 Mb region is associated with PTLS, which shows some phenotypical overlap with SMS, yet the clinical features of each syndrome are somewhat distinct. As in SMS, size of the duplication can vary between patients. The prevalence for SMS and PTLS is approximately 1 in 25,000 (Neira-Fresneda & Potocki 2015).

More information is available at: https://www.ncbi.nlm.nih.gov/books/NBK1310/ (SMS) and https://www.ncbi.nlm.nih.gov/books/NBK447920/ (PTLS).

This product is not CE/FDA registered for use in diagnostic procedures. The SALSA^® MLPA^® technique is covered by US patent 6,955,901 and corresponding patents outside the US. The purchase of this product includes a license to use only this amount of product solely for the purchaser’s own use.

Probemix content
P369-B1 Smith-Magenis contains 47 MLPA probes with amplification products between 127 and 483 nucleotides (nt). This includes one probe for the 17p12 chromosomal region and 29 probes for the 17p11.2 chromosomal region, of which ten target the RAI1 gene. Furthermore, five probes for the 2q37.3 chromosomal region are also present. In addition, twelve reference probes are included and detect twelve different 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.