General information
The SALSA MLPA Probemix P412-A3 Porphyria mix 2 is a research use only (RUO) assay for the detection of deletions or duplications in the FECH, UROS, UROD and CPOX genes. FECH, UROS and UROD are associated with Erythropoietic porphyria, while CPOX is linked to Acute hepatic porphyria. CPOX has been included in this probemix instead of the P411-B3 probemix, which contains ALAD, HMBS and PPOX, also linked to Acute hepatic porphyria, due to the limited number of probes which can be included in an MLPA probemix.

Porphyrias are a group of disorders characterised by accumulation of porphyrins and porphyrin precursors owing to enzymatic deficiencies of the haem biosynthetic pathway. They can be divided into acute hepatic porphyrias and erythropoietic porphyrias based on their clinical manifestations. Acute hepatic porphyrias are characterised by abdominal pain, neuropsychiatric symptoms and neuropathy. Erythropoietic porphyrias do not cause neurologic symptoms but are associated with photosensitive dermatologic eruptions and may be associated with additional hepatic injury and/or haemolysis (Simon, N.G et al. 2011).

Acute hepatic porphyrias consist of ALA dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), hereditary coproporphyria (HCP) and variegate porphyria (VP). Erythropoietic porphyrias comprise congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT) and the related hepatoerythropoietic porphyria and erythropoietic protoporphyria (EPP), see Table 1.

The FECH gene (11 exons) spans ~42 kb of genomic DNA and is located on 18q21.31, 53 Mb from the p-telomere.
The UROS gene (10 exons) spans ~35 kb of genomic DNA and is located on 10q26.2, 127 Mb from the p-telomere.
The UROD gene (10 exons) spans ~3.5 kb of genomic DNA and is located on 1p34.1, 45 Mb from the p-telomere.
The CPOX gene (7 exons) spans ~14 kb of genomic DNA and is located on 3q11.2, 99 Mb from the p-telomere.

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

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 P412-A3 Porphyria mix 2 contains 46 MLPA probes with amplification products between 130 and 489 nucleotides (nt). This P412-A3 includes the FECH, UROS , UROD and CPOX genes. 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.