General information
The SALSA MLPA Probemix P411 Porphyria mix 1 is a research use only (RUO) assay for the detection of deletions or duplications in the ALAD, HMBS and PPOX genes, which are associated with acute hepatic porphyria. The CPOX gene, which is also associated with acute hepatic porphyria, is included in the P412 Porphyria mix 2.

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 & Herkes, 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 ALAD gene (12 exons), spans ~15 kb of genomic DNA and is located on 9q32, 115 Mb from the p-telomere.
The HMBS gene (15 exons), spans ~8.7 kb of genomic DNA and is located on 11q23.3, 118 Mb from the p-telomere.
The PPOX gene, (13 exons) spans ~4.8 kb of genomic DNA and is located on 1q23.3, 159 Mb from the p-telomere.

More information is available at:
- https://omim.org/entry/125270?search=alad&highlight=alad
- https://omim.org/entry/609806?search=hmbs&highlight=hmbs
- https://omim.org/entry/600923?search=ppox&highlight=ppox-
- https://www.ncbi.nlm.nih.gov/books/NBK121283/
- https://www.ncbi.nlm.nih.gov/books/NBK1193/

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 P411-B3 Porphyria mix 1 contains 46 MLPA probes with amplification products between 131 and 495 nucleotides (nt). This includes one probe for each exon of the ALAD gene with the exception of exon 7 and 9, one probe for each exon of the HMBS gene with the exception of exon 2 (exon 2 is only present in transcript variant 2; NM_001024382), and one probe for each exon of the PPOX 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.