General Information: The SALSA MLPA
Probemix P289 LMX1B is a
research use only (RUO) assay for the detection of deletions or duplications in the
LMX1B gene, which is associated with Nail-patella syndrome.
The
LMX1B gene (8 exons) spans ~87 kb of genomic DNA and is located on chromosome 9q33, ~128 Mb from the p-telomere.
Nail patella syndrome (NPS) is an autosomal dominant disorder characterised by nail and skeletal malformations, nephropathy and glaucoma. The renal change resembles glomerulonephritis. Anomalies in a single gene,
LMX1B, underlie this disease. Genomic alterations affecting the function of the LMX1B gene are found in up to 91% of families with NPS (Ghoumid et al. 2016).
LMX1B encodes a transcription factor containing two zinc-binding LIM domains (exons 2&3) and a homeodomain (exons 4-6). This transcription factor is involved in multiple developmental processes, including those of the limbs and kidneys, which explains the pleiotropic effect of variation in this gene. The LIM domains are responsible for the interaction with other proteins, whereas the homeodomain binds to DNA. Absence or inactivation of the LIM domain inhibits the interaction with other transcription factors involved in DNA binding. Although clear genotype-phenotype associations have not been found for extrarenal manifestations, mutations in the homeobox are frequently associated with nephropathy (Harita et al. 2016). Along exhaustive information on
LMX1B sequence variation, MLPA revealed new LMX1B gene deletions (Bongers et al. 2008; Ghoumid et al. 2016). Please note that the MLPA probemix used by Bongers et al. is different from this P289 probemix.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1132.
Probemix content: The SALSA MLPA Probemix P289-A3 LMX1B contains 18 MLPA probes with amplification products between 165 and 319 nucleotides (nt). This includes eight probes for the
LMX1B gene, covering all exons. Furthermore, this probemix also contains a flanking probe for the 9q34 region. 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.mlpa.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, 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.mlpa.com.