General information:
The SALSA MLPA Probemix P343 Autism-1 is a research use only (RUO) assay for the detection of deletions or duplications in the 15q11-q13 chromosomal region (including UBE3A, GABRB3 and the 15q13 microdeletion region with CHRNA7), the 16p11 microdeletion region and the SHANK3 gene at 22q13, which are associated with autism.

Multiple studies postulate that at least some autism cases have a genetic basis and many different loci have been implicated in autism. This P343-C3 probemix contains MLPA probes for three of these chromosomal regions: the 15q11-q13 chromosomal region, the 16p11 microdeletion region and the SHANK3 gene. The TRPM1, KLF13 and CHRNA7 probes are located within the common 15q13 microdeletion region that has been described by Sharp et al. (2008). Please note that 15q13 duplications were identified not only in 12 out of 1223 epilepsy patients but also in 23 out of 3699 control samples (Helbig et al. 2009). 15q13 deletions were identified in 12 out of 1223 individuals with idiopathic generalized epilepsy and in 9 out of 3391 schizophrenia patients (International Schizophrenia Consortium 2008). No 15q13 deletions were detected in 3181 control samples.

Genomic imbalances of an approximately 600 kb region in 16p11.2 (29.5-30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. A recurrent microdeletion syndrome on 16p11.2-p12.2 has been described by Ballif et al. (2007). The phenotype included developmental delay. The size of the deletion is different in the five subjects described, however, all included the PALB2 and IL21R genes.

Please note that 15q11, 15q13 and 16p11.2 deletions and duplications have also been described in healthy individuals. Phenotype prediction for abnormalities detected in these regions is very difficult. The great majority of the probes targeting the 15q11 region differ from the probes present in the ME028 Prader-Willi-Angelman probemix. This P343 probemix may therefore also be useful for further characterisation of large deletions in Prader-Willi/Angelman patients.

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 P343-C3 Autism-1 contains 50 MLPA probes with amplification products between 121 and 500 nucleotides (nt). Within the 15q11 region, this includes two probes for the SNRPN-HB2-85 cluster, five probes for the UBE3A gene, two probes for ATP10A, seven probes for GABRB3 and two probes for OCA2. In addition, nine probes are present detecting 15q13 sequences, including three probes that are located within the common 15q13 microdeletion region. The 16p11.2 region is covered by 11 probes detecting sequences in the 28.9-30.2 Mb region. Three probes are included for the SHANK3 gene (exons 4, 15, and 22). In addition, ten 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.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.