General information: The SALSA MLPA Probemix P010 POLG is a research use only (RUO) assay for the detection of deletions or duplications in the genes POLG, POLG2, TWNK and SLC25A4, which are associated with autosomal disorders of mitochondrial DNA (mtDNA) maintenance.

The genes POLG (15q26.1), POLG2 (17q23.3), TWNK (10q24.31) and SLC25A4 (4q35.1) are involved in the replication of mtDNA, a process crucial to ensure cellular energy production. Pathogenic variants of those genes therefore lead to mtDNA depletion and/or accumulation of mtDNA deletions as well as energy deficiency within affected cells. Insufficient cellular energy production subsequently results in organ dysfunction. The most frequently affected organs and tissues are the brain, liver, skeletal muscle, peripheral nerves and gastrointestinal tract. MtDNA maintenance disorders are therefore classified into groups depending on the predominantly affected organ and range from early-onset pediatric encephalopathic syndromes to late-onset myopathy with chronic progressive external ophthalmoplegia.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK487393.

Probemix content: The SALSA MLPA Probemix P010-B1 POLG contains 44 MLPA probes with amplification products between 130 and 500 nucleotides (nt). This includes 23 probes for the POLG gene, three probes for the POLG2 gene, five probes for the TWNK gene, and four probes for the SLC25A4 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).