FANCONI ANEMIA (FA) is an autosomal recessive disorder characterised by physical abnormalities, bone marrow failure, and increased risk of malignancy. Mutations in several different genes can result in FA. Defects of the FANCA gene on chromosome 16q24.3 are the most frequent cause (60-70% of cases). Known defects of the FANCA gene include point mutations, small deletions/insertions and deletions of one or more complete exons.
The FANCA gene (43 exons), spans about 79 kb of genomic DNA and is located on chromosome 16q24.3, less than 500 kb from the 16q telomere. The P031-B2 and P032-B2 probemixes contain one probe for each FANCA exon. Probemix P031 contains 22 probes for different FANCA exons, as well as 10 reference probes detecting different autosomal chromosomal locations. Probemix P032 contains 21 probes for different FANCA exons and an additional flanking probe, as well as 11 reference probes detecting different autosomal chromosomal locations.
These SALSA® MLPA® probemixes are designed to detect deletions/duplications of one or more sequences of 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 these SALSA® MLPA® tests.