General information
The SALSA MLPA
Probemix P130 and P131 CCM are a
research use only (RUO) assay for the detection of deletions or duplications in the
KRIT1 (CCM1),
CCM2 and
PDCD10 (CCM3) genes, which are associated with Cerebral cavernous malformations (CCMs).
Cerebral cavernous malformations (CCMs) are vascular lesions of the brain that may lead to hemorrhage, seizures, and neurologic deficits. Most are linked to loss-of-function mutations in one of the aforementioned genes, that can either occur as sporadic events or are inherited in an autosomal dominant pattern with incomplete penetrance. Familial forms originate from germline mutations, often have multiple intracranial lesions that grow in size and number over time, and cause an earlier and more severe presentation.
The
KRIT1 gene (20 exons) spans ~47 kb of genomic DNA and is located on 7q21.2, ~92 Mb from the p-telomere. The
CCM2 gene (11 exons) spans ~76 kb of genomic DNA and is located on 7p13, ~45 Mb from the p-telomere. The
PDCD10 gene (9 exons) spans ~51 kb of genomic DNA and is located on 3q26.1, 167 Mb from the p-telomere.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1116/.
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 P130-A5 CCM mix-1 contains 34 MLPA probes with amplification products between 148 and 454 nt. The SALSA MLPA Probemix P131-B2 CCM mix-2 contains 31 MLPA probes with amplification products between 131 and 408 nt.
The P130 probemix contains probes for nine of the 20 exons of
KRIT1 and one probe for every exon of the
CCM2 gene (two probes for exon 3). In addition, 13 reference probes are included in this probemix, detecting several different autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes is available online (
www.mrcholland.com).
The P131 probemix contains probes for nine of the 20 exons of
KRIT1 and one probe for every exon of the
PDCD10 gene. One probe is located in intron 2 of the
PDCD10 gene and detects an alternative exon 2 in transcription variant 2 (NM_145859.1). In addition, 12 reference probes are included in this probemix, detecting several different autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes is 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.