General Information: The SALSA MLPA Probemix P089 TK2 is a research use only (RUO) assay for the detection of deletions or duplications in MPV17, DGUOK, SUCLG1, RRM2B, SUCLA2 and TK2 genes, which are associated with Mitochondrial DNA depletion syndromes.

Mitochondrial DNA (mtDNA) depletion syndromesare a clinically and genetically heterogeneous group of autosomal recessive disorders, characterized by a severe reduction in mtDNA content, which leads to decreased energy production in the affected tissues (El-Hattab and Scaglia 2013). The myopathic form, mtDNA depletion syndrome-2 (MTDPS2; OMIM # 609560) is associated with defects in the TK2 gene. This syndrome is characterized by muscle weakness with childhood onset, associated with depletion of mtDNA in skeletal muscle.

The encephalomyopathic form with methylmalonic aciduria, mtDNA depletion syndrome-9 (MTDPS9; OMIM # 245400) is caused by defects in the SUCLG1 gene, and it is characterized by hypotonia, muscle atrophy, feeding difficulties, lactic acidosis, and development delay, among other symptoms. Defects in the SUCLA2 gene causes mtDNA depletion syndrome-5 (MTDPS5; OMIM # 612073), which is difficult to distinguish from the MTDPS-9, being both associated with elevated methylmalonic aciduria.

A severe form with renal tubulopathy, mtDNA depletion syndrome-8A (MTDPS8A; OMIM # 612075) is linked to defects in the RRM2B gene. This syndrome is characterized by neonatal hypotonia, lactic acidosis, neurologic deterioration, and renal tubular involvement.

The hepatocerebral form, mtDNA depletion syndrome-3 (MTDPS3; OMIM # 251880) is linked to defects in the DGUOK gene, and it is characterized by progressive liver failure and neurological abnormalities with infancy onset, hypoglicemia, and increased lactate in body fluids. mtDNA depletion and decrease activity of the mtDNA-enconded respiratory chain complexes (I, II, IV and V) are present in the affected tissues. mtDNA depletion syndrome-6 (MTDPS6; OMIM # 256810), another hepatocerebral form, is caused by defects in the MPV17 gene. MTDPS6 is characterized by infantile onset of progressive liver failure, frequently leading to death in the first year of live, progressive neurologic involvement, including ataxia, hypotonia, dystonia and psychomotor regression is present in the infants that survive.

More information is available at: https://www.ncbi.nlm.nih.gov/books/NBK425223/;

https://www.omim.org/entry/609560 (TK2);
https://www.omim.org/entry/612073 (SUCLA2);
https://www.omim.org/entry/245400 (SUCLG1);
https://www.omim.org/entry/256810 (MPV17);
https://www.omim.org/entry/612075 (RRM2B);
https://www.omim.org/entry/251880 (DGUOK).

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 P089-B2 TK2 contains 49 MLPA probes with amplification products between 130 and 500 nt. This includes eight probes for the MPV17 gene, four probes for the DGUOK gene, four probes for the SUCLG1 gene, nine probes for the RRM2B gene, five probes for the SUCLA2 gene, ten probes for the TK2 gene. In addition, nine reference probes are included and detect nine 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, 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.mlpa.com.