General information
The SALSA MLPA Probemix P426 Cystinuria is a research use only (RUO) assay for the detection of deletions or duplications in the SLC3A1, PREPL and SLC7A9 genes, which are associated with cystinuria and hypotonia-cystinuria syndrome.

Cystinuria (OMIM #220100) is a disorder characterised by impaired reabsorption of cystine and dibasic amino acids (lysine, ornithine and arginine) in the brush border membrane of the proximal renal tubule and in the epithelial cells of the gastrointestinal tract. This eventually leads to accumulation of (cystine) crystals or stones in the kidneys and bladder, resulting in obstructive uropathy, pyelonephritis and sometimes renal failure. Thus far, two genes have been identified to cause cystinuria, SLC3A1 and SLC7A9, which encode parts of a transporter protein complex.

A large number of mutations in these genes have been identified in cystinuria, including deletions and duplications. Larger deletions affecting SLC3A1 might result in the so-called hypotonia-cystinuria syndrome (OMIM #606407). This autosomal recessive congenital disorder is associated with deletions of at least the SLC3A1 and nearby PREPL genes on chromosome 2p21. The main clinical features include a generalised hypotonia at birth, failure to thrive, intellectual disability and cystinuria.

SLC3A1 (~46 kb of genomic DNA; 10 exons) and PREPL (~41 kb of genomic DNA; 15 exons) are consecutively located on chromosome 2p21, about 44 Mb from the p-telomere. The SLC7A9 gene (13 exons) spans ~39 kb of genomic DNA and is located on chromosome 19q13.11, about 38 Mb from the p-telomere.

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 P426-A2 Cystinuria contains 48 MLPA probes with amplification products between 124 and 503 nucleotides (nt). This includes ten probes for the SLC3A1 gene (one for each exon), 13 probes for the SLC7A9 gene (one for each exon) and 12 probes for the PREPL gene (one probe for each exon with the exception of exon 3, 8 and 14). Furthermore, a single probe upstream and a single probe downstream are included for both chromosomal regions to determine the extent of a potential copy number change. 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.