General information
The SALSA MLPA Probemix P193 NPC1-NPC2-SMPD1 is a
research use only (RUO) assay for the detection of deletions or duplications in the
NPC1,
NPC2 and
SMPD1 genes, which are associated with Niemann-Pick diseases. This probemix can also be used to detect the presence of the wild type sequences of the
NPC1 p.Pro1007Ala (exon 20) and the
NPC1 p.Ile1061Thr (exon 21) mutations.
Niemann-Pick diseases are lipid storage disorders that manifest in a wide range of symptoms with varying severity. Characteristic, however, are an accumulation of harmful quantities of lipids in the spleen, liver, lungs, bone marrow and brain. Niemann-Pick diseases are inherited in an autosomal recessive manner. Mutations in the
SMPD1 gene (chromosome 11p15.4) cause Niemann-Pick disease types A and B. Niemann-Pick type A occurs in infants and is characterised by hepatosplenomegaly, failure to drive and progressive deterioration of the nervous system. Niemann-Pick type B usually presents in mid-childhood. Signs and symptoms are comparable to Niemann-Pick type A, but are less severe. Moreover, patients often suffer from recurrent lung infections and thrombocytopenia.
Approximately 94% of Niemann-Pick type C cases are caused by mutations in the
NPC1 (90%, chromosome 18q11.2) and
NPC2 (4%, chromosome 14q24.3) genes. Niemann-Pick type C usually becomes apparent in mid-to-late childhood with onset of ataxia, vertical supranuclear gaze palsy and dementia.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1296/ (Niemann-Pick type C) and
https://www.ncbi.nlm.nih.gov/books/NBK1370/ (Niemann-Pick types A and B)
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 P193-B3 NPC1-NPC2-SMPD1 contains 49 MLPA probes with amplification products between 130 and 493 nucleotides (nt). This includes 26 probes for the
NPC1 gene, five probes for the
NPC2 gene, and six probes for the
SMPD1 gene. Furthermore, this probemix also contains two probes detecting the wild type sequences of the
NPC1 p.Pro1007Ala (exon 20) and the
NPC1 p.Ile1061Thr (exon 21) mutations, which will only generate a signal when the mutation is present. 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.