PT  - JOURNAL ARTICLE
AU  - Zyla, Roman E
AU  - Hodgson, Anjelica
TI  - Gene of the month: FH
AID  - 10.1136/jclinpath-2021-207830
DP  - 2021 Oct 01
TA  - Journal of Clinical Pathology
PG  - 615--619
VI  - 74
IP  - 10
4099  - http://jcp.bmj.com/content/74/10/615.short
4100  - http://jcp.bmj.com/content/74/10/615.full
SO  - J Clin Pathol2021 Oct 01; 74
AB  - Fumarate hydratase (FH), encoded by the FH gene, is an enzyme which catalyses the conversion of fumarate to L-malate as part of the tricarboxylic acid cycle. Biallelic germline mutations in FH result in fumaric aciduria, a metabolic disorder resulting in severe neurological and developmental abnormalities. Heterozygous germline mutations in FH result in hereditary leiomyomatosis and renal cell carcinoma, a cancer predisposition syndrome. FH deficiency has multiple oncogenic mechanisms including through promotion of aerobic glycolysis, induction of pseudohypoxia, post-translational protein modification and impairment of DNA damage repair by homologous recombination. FH-deficient neoplasms can present with characteristic morphological features that raise suspicion for FH alterations and also frequently demonstrate loss of FH immunoreactivity and intracellular accumulation of 2-succinocysteine, also detected by immunohistochemistry.