General information: The SALSA MLPA Probemix P198 FH is a research use only (RUO) assay for the detection of deletions or duplications in the fumarate hydratase (FH) gene, which is associated with FH tumour predisposition syndrome and FH deficiency.

FH tumour predisposition syndrome (also known as hereditary leiomyomatosis and renal cell cancer, HLRCC) is an autosomal dominant tumour syndrome characterized by leiomyomas in the skin and uterus. A subset of patients develops renal cell cancer (Smit et al. 2011). In the exceptional case of autosomal recessive inheritance, homozygous FH mutations result in FH deficiency (also known as fumarase deficiency or fumaric aciduria), which causes neonatal and early infantile encephalopathy. FH deficiency is characterized by poor feeding, failure to thrive, hypotonia, lethargy and seizures. FH deficiency is often fatal in early childhood.

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 protein encoded by FH is an enzymatic component of the Krebs cycle. It catalyzes the conversion of fumarate to malate.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1252/ (FH tumour predisposition syndrome) and https://www.ncbi.nlm.nih.gov/books/NBK1506/ (FH deficiency).

This SALSA MLPA Probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.

Probemix content: The SALSA MLPA Probemix P198-A4 FH contains 19 MLPA probes with amplification products between 142 and 300 nucleotides (nt). This includes 10 probes for the FH gene, one probe for each exon. In addition, nine reference probes are included that detect autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (www.mlpa.com).

This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mlpa.com.