Gene of the month: FH

Fumarate hydratase (FH), encoded by the FH gene, is an enzyme which catalyses conversion of fumarate to L-malate as part tricarboxylic acid cycle. Biallelic germline mutations in result fumaric aciduria, a metabolic disorder resulting severe neurological and developmental abnormalities. Heterozygous hereditary leiomyomatosis renal cell carcinoma, cancer predisposition syndrome. deficiency has multiple oncogenic mechanisms including through promotion aerobic glycolysis, induction pseudohypoxia, post-translational protein modification impairment DNA damage repair homologous recombination. FH-deficient neoplasms can present with characteristic morphological features that raise suspicion for alterations also frequently demonstrate loss immunoreactivity intracellular accumulation 2-succinocysteine, detected immunohistochemistry.