General information: The SALSA MLPA Probemix P484 ALPL is a
research use only (RUO) assay for the detection of deletions or duplications in the
ALPL gene, which is associated with hypophosphatasia (HPP).
HPP is a rare inherited metabolic disorder that is primarily characterised by reduced bone and dental mineralization. Severity and penetrance vary greatly: from stillbirth due to profound skeletal hypomineralization to adult-onset dental problems or arthropathies without bone disease. Severe forms are autosomal recessive with an estimate prevalence of 1:100,000-300,000; while less severe forms may be autosomal recessive or dominant and the prevalence may reach 1:6,000. Alleles associated with less severe dominant forms can have incomplete penetrance (Millan and Whyte 2016, Mornet 2017, Mornet 2018). Known pathogenic
ALPL mutations cause loss of function of the tissue non-specific alkaline phosphatase (TNSALP) protein. Approximately 2-3% of pathogenic
ALPL variants are deletions of one or more exons, but pathogenic whole gene deletions have not been found (Spentchian et al. 2006, Taillandier et al. 2017).
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1150/
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 P484-A1 ALPL contains 25 MLPA probes with amplification products between 130 and 310 nucleotides (nt). This includes 15 probes for the
ALPL gene one probe for each of the 12 exons, two additional probes closely up- and downstream of exon 1, and a second probe for exon 12. In addition, ten 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.