General information
The SALSA MLPA
Probemix P409 RASA1-EPHB4 is a
research use only (RUO) assay for the detection of deletions or duplications in the
RASA1 and
EPHB4 genes, which are associated with capillary malformation-arteriovenous malformation (CM-AVM) syndrome.
CM-AVM syndrome is a disorder of the vascular system that is characterised by multiple cutaneous capillary malformations (CMs) that are mostly found on the face, arms and legs. Some affected individuals also have one or more arteriovenous malformations (AVMs) and/or arteriovenous fistulas (AVFs), fast-flow vascular malformations that typically arise in the skin, muscle, bone, spine and brain. Depending on their location in the body, these abnormalities could lead to life-threatening complications including haemorrhage and heart failure. The presence of AVMs/AVFs can also cause soft tissue and skeletal hypertrophy, resulting in limb overgrowth. This phenotype of CM-AVM syndrome is called Parkes Weber syndrome.
CM-AVM is an autosomal-dominant disease that is caused by mutations in the
RASA1 and
EPHB4 genes (Eerola et al. 2003; Amyere et al. 2017). The
RASA1 gene encodes Ras GTPase-activating protein 1, a protein involved in a wide variety of processes including regulation of cellular differentiation and proliferation, and cytoskeletal reorganisation. Ras GTPase-activating protein 1 is thought to have an important function in the development of the vascular system. The
RASA1 gene (25 exons) spans ~124 kb of genomic DNA and is located on chromosome 5q14.3, about 87 Mb from the p-telomere. The
EPHB4 gene encodes the ephrin type-B receptor 4, a transmembrane receptor that is expressed in venous endothelial cells during vascular development. Mutations in
EPHB4 hamper EPHB4-EphrinB2 signalling, which leads to abnormal differentiation of endothelial cells and disorganized vascular development. The
EPHB4 gene (17 exons) spans ~25 kb of genomic DNA and is located on chromosome 7q22.1, about 100 Mb from the p-telomere.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK52764/.
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 P409-B1 RASA1-EPHB4 contains 50 MLPA probes with amplification products between 124 and 499 nucleotides (nt). This includes 26 probes for the
RASA1 gene, one probe for each exon and two probes for exon 1, and 16 probes for the
EPHB4 gene, one probe for each exon with the exception of exon 10. 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. 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.