Burnichon et al. (2010) reported a 32-year-old woman who developed a catecholamine-secreting extraadrenal paraganglioma. Clinical features included hypertension and hyperadrenergic symptoms, such as dizziness, tachycardia, and sweating. She had high concentrations of urinary normetanephrine, norepinephrine, and chromogranin A. ... Burnichon et al. (2010) reported a 32-year-old woman who developed a catecholamine-secreting extraadrenal paraganglioma. Clinical features included hypertension and hyperadrenergic symptoms, such as dizziness, tachycardia, and sweating. She had high concentrations of urinary normetanephrine, norepinephrine, and chromogranin A. The symptoms resolved after surgical resection of the tumor. There was no family history of the disorder.
In a woman with an extraadrenal paraganglioma, Burnichon et al. (2010) identified a heterozygous germline mutation in the SDHA gene (R589W; 600857.0005). Tumor tissue showed loss of heterozygosity (LOH) at the SDHA locus. In vitro functional expression studies ... In a woman with an extraadrenal paraganglioma, Burnichon et al. (2010) identified a heterozygous germline mutation in the SDHA gene (R589W; 600857.0005). Tumor tissue showed loss of heterozygosity (LOH) at the SDHA locus. In vitro functional expression studies in the yeast homolog showed that the mutation resulted in a loss of SDH activity and rendered the mutant SDHA protein more susceptible to proteolysis. Studies of tumor tissue from the patient showed lack of SDHA and SDHB (185470) expression. Transcriptome analysis of the patient's tumor showed a similar pattern as that of other SDH-subunit mutated paraganglioma tumors, including stabilization of HIF1A (603348), consistent with activation of a pseudohypoxic pathway and angiogenesis. The findings indicated that SDHA, like other SDH subunits, can act as a tumor suppressor gene. Analysis of a large series of paragangliomas and pheochromocytomas found LOH at the SDHA locus in only 9 (4.5%) of 202 tumors, suggesting that it is an infrequent event.