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 (including UBE3A, GABRB3 and the 15q13 microdeletion region with CHRNA7), the 16p11 microdeletion region and the SHANK3 gene at 22q13.
Within the 15q11 region, two probes have been included for the SNRPN-HB2-85 cluster, five for the UBE3A gene, two for ATP10A, seven for GABRB3 and two for OCA2. The great majority of these probes 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. In addition, nine probes are present detecting 15q13 sequences, including three probes that are located within the common 15q13 microdeletion region described by Sharp A.J. et al (Nature Genetics 2008, 40:322-328).
The 16p11.2 region is covered by 11 probes detecting sequences in the 28.9-30.2 Mb region. 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.
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 SHANK3 gene (22 exons) spans ~58 kb of genomic DNA and is located on 22q13.33, 49 Mb from the p-telomere. Three probes are included for SHANK3 gene (exons 3, 14, and 21).
Finally, ten reference probes are included in this probemix, detecting different autosomal chromosomal locations.
This SALSA® MLPA® probemix is designed to detect/duplications of one or more sequences in the above mentioned chromosomal regions in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. Finally, note that most defects in these regions are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.