General information
The SALSA MLPA Probemix P080 Craniofacial is a research use only (RUO) assay for the detection of deletions or duplications in the FGFR1, FGFR2, FGFR3, TWIST1, MSX2, ALX4, ALX3, ALX1, RUNX2 and EFNB1 genes, which is associated with several craniofacial disorders. This probemix can also be used to detect the presence of the wild-type sequences of the FGFR2 c.755C>G and the FGFR3 c.749C>G point mutations

The FGFR1, FGFR2 and FGFR3 genes encode growth factors and cause a diverse group of skeletal disorders. In general, mutations in FGFR1 and FGFR2 mostly cause craniosynostosis (premature fusion of the cranial sutures). Dwarfing syndromes are often associated with FGFR3 mutations.
Deletion of the TWIST1 gene is the cause of disease in an estimated 11% of Saethre-Chotzen syndrome patients. Also included is a probe for the TWISTNB (TWIST nearby) gene located at a distance of ~500 kb from TWIST1. Large deletions of the TWIST region often result in mental retardation.

Dosage of the MSX2 gene is critical for human skull development. Enlarged parietal foramina and craniosynostosis can result, respectively, from loss and gain of activity in an MSX2 pathway of calvarial osteogenic differentiation.

Mutations in ALX4 can result in parietal foramina as well as craniosynostosis. Potocki-Shaffer syndrome, also known as the proximal 11p deletion syndrome, is a contiguous gene syndrome caused by deletion of the 11p13-p11 region. Mutations in the ALX3 gene can result in frontonasal dysplasia. The ALX1 gene is known to be essential for normal skull bone development; null mice are born with severe craniofacial defects such as a lacking cranium.
Defects in the RUNX2 gene cause the dominant disorder cleidocranial dysplasia.
Loss-of-function mutations in the EFNB1 gene cause craniofrontonasal syndrome.

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

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 P080-C2 Craniofacial contains 48 MLPA probes with amplification products between 122 and 504 nt. This includes 39 probes for the different genes involved in craniofacial disorders, as described in tables 1 and 2. In addition, nine reference probes are included that detect different 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.