Choose your country to see the products for your location

SALSA MLPA Probemix P242 Pancreatitis

Pancreatitis, hereditary (HP)

Region: PRSS1 7q34; SPINK1 5q32; CTRC 1p36.21

MLPA | Improved
General information
SALSA® MLPA® Probemix P242 Pancreatitis is a research use only (RUO) assay for the detection of deletions, duplications or genomic rearrangements in the CTRC, SPINK1, PRSS1 and PRSS2 genes, which are associated with hereditary pancreatitis. This probemix includes probes for the TRD-AS1 gene as an aid to interpret PRSS1 and PRSS2 copy numbers when larger regions are affected (see Appendix 1). This probemix also detects the presence of the SPINK1 p.N34S (c.101A>G), PRSS1 p.N29I (c.86A>T) and PRSS1 p.R122H (c.365G>A) point mutations.

Hereditary Pancreatitis (HP; OMIM # 167800) is characterised by recurrent episodes of inflammation of the pancreas that progress to chronic pancreatitis. HP has an autosomal dominant pattern of inheritance and is defined by two or more individuals with pancreatitis in two or more generations of a family, or pancreatitis associated with a known germline pathogenic variant.

PRSS1 encodes trypsin-1 (cationic trypsinogen), a major pancreatic digestive serine peptidase enzyme, which is produced and secreted by the pancreas. PRSS1 pathogenic variants typically result in a trypsin protein that is either prematurely activated, while it is still in the pancreas, or resistant to degradation. Duplication of PRSS1, leading to an increase of the protein, also causes HP. Duplication and triplication of a ~605-kb segment containing PRSS1 and PRSS2 have been described (Chauvin et al. 2009). Furthermore, gene conversion between PRSS1 and PRSS2 has been reported (Nemeth and Sahin-Tóth 2014, Rygiel et al. 2015). In 90% of the cases, hereditary pancreatitis is caused by two point mutations in the PRSS1 gene, R122H (~65%) and N29I (~25%) (Nemeth and Sahin-Tóth 2014). Gene conversion between PRSS1 and PRSS2 exon 2 and intron 2 can occur, resulting in the N29I mutation together with N54S, a non-pathogenic mutation (Teich et al. 2005). Masson et al. (2008a) identified a hybrid PRSS1/PRSS2 duplication in which exons 1 and 2 were derived from PRSS2 and exons 3 to 5 from PRSS1, which also contained the PRSS1 N29I mutation. In less than 6% of the cases, HP is caused by PRSS1 (large) deletions/duplications.

SPINK1 encodes the serine protease inhibitor Kazal-type 1. Pathogenic variants in SPINK1 are associated with increased risk of pancreatitis and have been identified in approximately 20% of families with hereditary pancreatitis, without a PRSS1 germline pathogenic variant. The risk for developing acute pancreatitis is highly increased when the N34S mutation in SPINK1 is present (Koziel et al. 2015).

CTRC encodes chymotrypsin C (CTRC), a low-abundance pancreatic digestive enzyme that is synthetized with PRSS1. CTRC is important for the degradation of the prematurely activated trypsin within the pancreas. Pathogenic variants of CTRC have been associated with chronic pancreatitis (Masson et al. 2008b).

While identification of a heterozygous PRSS1 pathogenic variant confirms a diagnosis of hereditary pancreatitis, the presence of isolated pathogenic variants in the SPINK1 or CTRC genes is insufficient to cause pancreatitis (Masson et al. 2013).

The CTRC gene (8 exons) spans ~11 kb of genomic DNA and is located on 1p36.21, about 15 Mb from the p-telomere. The SPINK1 gene (4 exons) spans ~7.1 kb of genomic DNA and is located on 5q32, about 148 Mb from the p-telomere. The PRSS1 gene (5 exons) spans ~3.6 kb of genomic DNA and is located on 7q34, about 143 Mb from the p-telomere. The PRSS2 gene (5 exons) spans ~3.6 kb of genomic DNA and is located on 7q34, about 143 Mb from the p-telomere. The TRD-AS1 gene (5 exons) spans ~104 kb of genomic DNA and is located on 14q11.2, about 22 Mb from the p-telomere.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK190101 and https://www.ncbi.nlm.nih.gov/books/NBK84399 .

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

P242-D1 Pancreatitis contains 41 MLPA probes with amplification products between 124 and 409 nucleotides (nt). This includes eight probes for the CTRC gene, six probes for the SPINK1 gene (one of which is a flanking probe), nine probes for the PRSS1 gene (one of which is a flanking probe), five probes for the PRSS2 gene (three of which are flanking probes) and three probes for the TRD-AS1 gene. These include three probes specific for the SPINK1 p.N34S (c.101A>G), PRSS1 p.N29I (c.86A>T) and PRSS1 p.R122H (c.365G>A) mutations which will only generate a signal when the mutation is present. In addition, ten 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 .

Sample DNA
Sample DNA developed for this product:
  • SD099 Binning DNA - included with this probemix.
The product description of this Sample DNA can be found on this page under Online available downloads > Other product documentation.

Order Items

Probemix

Item no.
Description
Technology
Price
P242-025R
SALSA MLPA Probemix P242 Pancreatitis – 25 rxn
€ 286.00
P242-050R
SALSA MLPA Probemix P242 Pancreatitis – 50 rxn
€ 560.00
P242-100R
SALSA MLPA Probemix P242 Pancreatitis – 100 rxn
€ 1096.00

Required Reagents (Sold Separately)

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM (6 vials)
€ 348.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
€ 348.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
€ 1600.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
€ 1600.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
€ 6152.00

Related Products

SALSA MLPA Probemix P091 CFTR

Contains probes for the CFTR gene, related to chronic pancreatitis.

Sign in

Don't have an account? Create one

Forgot password?

Select Your Country

Choose your country to see the products for your location

Improvements

15 target probes added/replaced, CASP2 & BRAF flanking probes removed, 8 reference probes replaced