General Information: The SALSA MLPA
Probemix P158 JPS is a
research use only (RUO) assay for the detection of deletions or duplications in the
BMPR1A,
SMAD4, and
PTEN genes, which are associated with Juvenile Polyposis Syndrome (JPS).
JPS is an autosomal dominant condition characterised by the development of various types of tumours. The diagnosis is based on the occurrence of hamartomatous gastrointestinal polyps that turn into malignant lesions in approximately 20% of the cases. Defects in the
BMPR1A gene on chromosome 10q23.2 and the
SMAD4 gene on chromosome 18q21.2 are the main causes of juvenile polyposis. Defects in the
PTEN gene on chromosome 10q23.31 can result in Cowden syndrome which has some phenotypic resemblance to JPS. For this reason, probes for the
PTEN gene are also included. More
PTEN probes are present in the P225 PTEN probemix. Due to the presence of pseudogenes in the human genome, it was necessary to locate several probes in intron sequences close to the exons.
A study revealed a
SMAD4 retrotransposon in a breast cancer case using NGS data and multiple analytical methods (Patil et al. 2015). Another recent investigation on
SMAD4 supports the presence of a pseudogene, which has the potential to confound the interpretation of genetic testing results, as only mutations in the native gene are clinically significant (Mancini et al. 2015; Millson et al. 2015).
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1469/.
Probemix content: The SALSA MLPA Probemix P158-D1 JPS contains 51 MLPA probes with amplification products between 118 and 499 nt. This includes 15 probes for all 13 exons of the
BMPR1A gene, with two probes for exon 1 and 3, and 15 probes for all 12 exons of the
SMAD4 gene, including four probes for exon 1. Furthermore, 11 probes for all nine exons of the
PTEN gene are included, with two probes for exon 3 and one probe upstream of the gene. In addition, ten reference probes are included and detect different autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes is 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.