Fumarase deficiency (also known as Fumarate Hydratase Deficiency or Fumaric Aciduria) is a rare recessive encephalopathy characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Additionally, some patients have dysmorphic facial features. Mutations in the fumarate hydratase (FH) gene on chromosome 1 are the cause of fumarase deficiency. The protein encoded by this gene is an enzymatic component of the Krebs cycle. It catalyzes the conversion of fumarate to malate.
The FH gene (10 exons) spans ~22 kb of genomic DNA and is located on chromosome 1q43, about 240 Mb from the p-telomere. The P198-A3 probemix contains one probe for each exon of the FH gene. In addition, 9 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 gene 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.