General information
The SALSA MLPA Probemix P275 MAPT-GRN is a research use only (RUO) assay for the detection of deletions or duplications in the MAPT, GRN, and CRHR1 genes. This probemix can also be used to detect the presence of wildtype allele of the MAPT P301L (c.1853C>T) point mutation.

The MAPT gene encodes the microtubule-associated protein tau. Mutations in MAPT have been associated with several neurodegenerative disorders, such as frontotemporal dementia with parkinsonism, progressive supranuclear palsy, corticobasal degeneration, Pick disease, and dementia with epilepsy.

The MAPT gene (14 exons) spans ~134 kb of genomic DNA and is located on chromosome 17q21.31, 41 Mb from the p-telomere. The region on 17q21, which encompasses the MAPT and CRHR1 genes, is flanked by repeated DNA elements and is often (20% in Europeans) present in inverted position. The Koolen-de Vries syndrome (OMIM 610443), characterized by developmental delay and mild to moderate intellectual disability, can be caused by a microdeletion in this region. Loss of the KANSL1 gene, which is located 7 kb downstream of the MAPT gene, accounts for the features of that syndrome. Duplication of the 17q21 region can result in psychomotor developmental delay (Kirchhoff et al. 2007; Grisart et al. 2009).

The GRN (PGRN) gene (13 exons), spans ~8 kb of genomic DNA and is located on chromosome 17q21.31, 40 Mb from the p-telomere. Defects in the GRN gene cause frontotemporal lobar degeneration.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1371/.

Probemix content
The SALSA MLPA Probemix P275-C4 MAPT-GRN contains 41 MLPA probes with amplification products between 148 and 490 nucleotides (nt). This includes 14 probes for the MAPT gene, one probe for each exon including one probe specific for the wildtype allele of the P301L (c.1853C>T) point mutation which will only generate a signal when the wildtype allele is present. Furthermore, five probes for the GRN gene, five probes for the CRHR1 gene, seven probes for other genes in the 17q21 region, and one probe each for the 17q11 and 17q12 regions are included in this probemix. In addition, eight 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 (see table below). 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.