It’s All in the Genes:
Hereditary Cancer and SDHA
July 14, 2021
DELRAY BEACH, FL – The SDHA gene codes for the catalytic subunit of the succinate dehydrogenase (SDH) enzyme, which functions in the citric acid cycle converting succinate to fumarate. Reduced function results in the upregulation of genes involved in neoplasia, increased ROS levels and mitochondrial dysfunction.1 Variations in the SDHA genes are related to Hereditary paraganglioma-pheochromocytoma, Gastrointestinal stromal tumor (GIST) and Leigh Syndrome.2
More than 75 percent of GISTs indicate SDH deficiency and are often associated with germline variants that affect SDHA, SDHB, SDHC or SDHD, which code for all the functional subunits of SDH.1 A recent study in the European Journal of Human Genetics describes an instance of multilocus inherited neoplasia alleles syndrome (MINAS), where familial GISTs were a result of multiple germline variations, including variations in SDHA and PALB2.1 Early identification of these patients with multiple variations is vital to their long-term care, familial care and reproductive choices.
Genetics Institute of America’s Comprehensive Hereditary Cancer Panel provides a complete analysis of 52 genes associated with hereditary breast, ovarian, uterine, bladder, colorectal, pancreatic, prostate, melanoma, gastric and other inherited cancer. SDHA, SDHB, SDHC, SDHD and PALB2 are screened within this test to give a complete look at a patient’s hereditary cancer predisposition and aid in guiding their individualized health and treatment plan.
Whitworth J, Casey RT, Smith PS, et al. Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2 [published online ahead of print, 2021 Apr 15]. Eur J Hum Genet. 2021;10.1038/s41431-021-00862-5. doi:10.1038/s41431-021-00862-5
SDHA gene: MedlinePlus Genetics. MedlinePlus. https://medlineplus.gov/genetics/gene/sdha/. Published August 18, 2020. Accessed June 11, 2021.