The SALSA MLPA
Probemix P080 Craniofacial is a research use only (RUO)
assay for the detection of deletions or duplications in the FGFR1
genes, which are 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.
genes encode growth factors and cause a diverse group of skeletal disorders. In general, mutations in FGFR1
mostly cause craniosynostosis (premature fusion of the cranial sutures). Dwarfing syndromes are often associated with FGFR3
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.
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 and detect different autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes is available online (www.mlpa.com
This probemix contains nine quality control fragments generating amplification products between 64 and 121 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.mlpa.com