General information
The SALSA MLPA
Probemix P028 FHL is a
research use only (RUO) assay for the detection of deletions or duplications in the
UNC13D,
PRF1 and
STX11 genes, which are associated with familial haemophagocytic lymphohistiocytosis (FHL).
FHL is a rare autosomal recessive disorder associated with perforin (
PRF1) deficiency or a disruption of perforin delivery, which lead to impaired immune activity of cytotoxic T lymphocytes and Natural Killer (NK) cells (Brennan et al. 2010). To compensate for the loss of functional T cells and NK cells, an exaggerated immune response is triggered that is characteristic for FHL. Massive organ infiltration by activated lymphocytes and macrophages can be observed. Other symptoms include persistent fever, hepatosplenomegaly and cytopenia. First episodes occur mostly during infancy, with a rapidly fatal outcome if untreated. Five FHL subtypes (FHL1, FHL2, FHL3, FHL4, FHL5) have been described. Mutations in the
UNC13D gene are associated with FHL3, defects in the
PRF1 gene cause FHL2, and
STX11 mutations cause FHL4.
The
UNC13D gene (32 exons) spans ~17 kb of genomic DNA and is located on chromosome 17q25.1, ~71 Mb from the p-telomere. The
PRF1 gene (3 exons) spans ~5.4 kb of genomic DNA and is located on chromosome 10q22.1, 72 Mb from the p-telomere. The
STX11 gene (2 exons) spans ~41 kb of genomic DNA and is located on chromosome 6q24.2, ~145 Mb from the p-telomere.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1444/.
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 P028-B2 FHL contains 44 MLPA probes with amplification products between 130 and 481 nucleotides (nt). This includes 30 probes for the
UNC13D gene, three probes for the
PRF1 gene and two probes for the
STX11 gene. 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.