The SALSA MLPA
Probemix P188 22q13 is a research use only (RUO)
assay for the detection of deletions or duplications in the 22q12 and 22q13 chromosomal regions. A partial 22q13 deletion is associated with the Phelan-McDermid syndrome (22q13.3 deletion syndrome).
The Phelan-McDermid syndrome (PHMDS; OMIM 606232) is characterised by severe expressive language delay and mild mental retardation. Most patients display hypotonia and normal to accelerated growth. PHMDS, caused by a deletion of 22q13.3 that includes at least part of SHANK3
or a pathogenic variant in SHANK3
, is inherited in an autosomal dominant manner. Most cases are however not inherited, but occur de novo
. Haploinsufficiency of the SHANK3
gene is very likely the cause of the major neurological features associated with PHMDS. Deletion of additional genes probably causes more complex phenotypes in individuals with larger deletions. The most common cause of PHMDS are terminal chromosomal deletions (including SHANK3
), which are extremely variable in size: ranging from <50 kb to >9 Mb. Interstitial deletions, intragenic deletions/pathogenic variants in SHANK3
, ring chromosomes, and unbalanced translocations have also been described as causes of PHMDS.
More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1198/
The SALSA MLPA Probemix P188-C1 22q13 contains 46 MLPA probes with amplification products between 130 and 500 nucleotides (nt). This includes 30 probes for the 22q13 chromosomal region and four probes for the 22q12 chromosomal region. Four of the 22q13 probes detect sequences in the SHANK3
gene. In addition, 12 reference probes are included which detect 12 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 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.mlpa.com