Migraine is a common neurological disorder that affects up to 18% of the general population. Familial hemiplegic migraine (FHM) is a rare autosomal dominantly inherited subtype of migraine with aura. In FHM, the aura usually consist of a phase with hemiparesis accompanied by typical aura symptoms, including visual, sensory or speech disturbances, followed by a headache phase. Roughly half of the FHM families are linked to chromosome 19p13 (FHM1; CACNA1A), other FHM families are linked to chromosome 1q23 (FHM2; ATP1A2).
The ATP1A2 gene (23 exons) spans ~28 kb of genomic DNA and is located on 1q23.2, 160 Mb from the p-telomere. The CACNA1A gene (47 exons) spans ~300 kb of genomic DNA and is located chromosome 19p13, ~13 Mb from the p-telomere. The P348-B1 probemix contains one probe for each exon of the ATP1A2 gene with the exception of exons 18 and 23, and contains probes for 15 of the 47 exons of CACNA1A. In addition, nine reference probes are included in this probemix, detecting several 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.