Epilepsy can be caused by mutations in one or more exons of the KCNQ3, CHRNA4, EPM2A, NHLRC1 (also known as EPM2B or malin) and CHRNB2 genes.
Defects in the KCNQ3 gene can cause benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2). The KCNQ3 gene comprises 15 exons and spans ~360 kb of genomic DNA on chromosome 8q24.22. This probemix contains 15 probes for KCNQ3 exons. Two probes are present for exon 1, no probe is present for exon 7.
The CHRNA4 gene comprises 6 exons, spanning ~18 kb of genomic DNA on chromosome 20q13.33. Mutations in this gene appear to account for a small proportion of the cases of nocturnal frontal lobe epilepsy. This probemix contains one probe for each CHRNA4 exon.
Mutations in the EPM2A gene have been associated with myoclonic epilepsy of Lafora. The EPM2A gene encodes the laforin protein, comprises 4 exons and spans ~111 kb of genomic DNA on chromosome 6q24.3. This probemix contains probes for each of the EPM2A exons.
The NHLRC1 (EPM2B) gene encoding the malin protein, comprises 1 exon and spans ~1.2 kb of genomic DNA on chromosome 6p22.3. Mutations in NHLRC1 cause progressive myoclonus epilepsy. Two probes for NHLRC1 have been included in this probemix. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy.
The CHRNB2 gene comprises 6 exons and spans ~12.2 kb of genomic DNA on chromosome 1q21.3. This probemix contains probes for two CHRNB2 exons.
In addition, this probemix contains two probes for the KCNQ1 gene. The KCNQ1 gene comprises 16 exons, spanning ~404 kb of genomic DNA on chromosome 11p15.5-4.
Furthermore, this P197-A3 probemix contains 8 reference probes detecting different autosomal chromosomal locations.
This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned genes 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. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.