General information: The SALSA MLPA Probemix P099 GCH1-TH-SGCE-PRRT2 is a research use only (RUO) assay for the detection of deletions or duplications in the GCH1, TH, SGCE and PRRT2 genes, which are associated with autosomal dominant dopa-responsive dystonia, autosomal recessive dopa-responsive dystonia, myoclonus-dystonia syndrome and paroxysmal movement disorders, respectively.

Autosomal dominant dopa-responsive dystonia (also known as autosomal dominant Segawa syndrome or GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia; OMIM #128230) is characterised by postural and motor disturbances showing marked diurnal fluctuation (Segawa et al. 1976). The disorder is caused by a mutation in the GCH1 gene encoding GTP cyclohydrolase I. The GTP cyclohydrolase I enzyme is rate-limiting in the conversion of GTP to BH4, which is a cofactor for tyrosine hydroxylase (TH). TH is the rate-limiting enzyme for dopamine synthesis. The GCH1 gene has 6 exons, spans ~61 kb of genomic DNA and is located on chromosome 14q22.2, ~55 Mb from the p-telomere. More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1508/

The autosomal recessive form of dopa-responsive dystonia (also known as autosomal recessive Segawa syndrome or Tyrosine hydroxylase deficiency; OMIM #605407) is commonly caused by deficiency of TH (De Lonlay et al. 2000). TH is involved in the conversion of tyrosine to dopamine. As the rate-limiting enzyme in the synthesis of catecholamines, tyrosine hydroxylase has a key role in the physiology of adrenergic neurons. The TH gene is located in the Beckwith-Wiedemann syndrome (BWS) critical region (Gu et al. 2002) on chromosome 11p15.5. The TH gene has 14 exons and spans ~8 kb of genomic DNA, ~2 Mb from the p-telomere. More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1437/

Myoclonus-dystonia syndrome (OMIM #159900) is caused by mutations in the SGCE gene encoding epsilon-sarcoglycan. The SGCE gene has 11 exons, spans ~71 kb of genomic DNA and is located on chromosome 7q21.3, ~94 Mb from the p-telomere. More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1414/

Several paroxysmal movement disorders have been associated with the PRRT2 gene. In addition to these PRRT2-associated paroxysmal movement disorders, the gene has also been linked to other movement disorders and seizures. The PRRT2 gene has 4 exons, spans ~4 kb of genomic DNA and is located on chromosome 16p11.2, ~29 MB from the p-telomere. More information is available at https://www.ncbi.nlm.nih.gov/books/NBK475803/

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 P099-D1 GCH1-TH-SGCE-PRRT2 contains 39 MLPA probes with amplification products between 130 and 445 nucleotides (nt). This includes seven probes for GCH1, six probes for TH, thirteen probes for SGCE and five probes for PRRT2. In addition, eight 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 (see table below). 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