University of Utah scientists have identified a genetic mutation linked to hereditary form of a rare neuroendocrine tumor called paraganglioma (PGL).
Paragangliomas are rare, generally benign tumors that arise from cells called glomus cells, which are located along blood vessels and play a role in regulating blood pressure and blood flow.
According to the researchers, the gene, called hSDH5, is required for activation of an enzyme complex that plays a critical role in the chemical reactions that take place within cells to convert biochemical energy into usable energy.
The researchers used yeast Saccharomyces cerevisiae, in order to study mitochondrial functions before going back to humans and determining whether what we learned in yeast was also relevant to humans.
They first characterized a mitochondrial protein called Sdh5 in yeast and then moved on to study its potential role in human disease.
Rutter and his colleagues discovered that, in yeast, the Sdh5 protein is needed for the SDH complex to function normally.
"The amino acid sequence of yeast Sdh5 is 44 percent identical to its human counterpart, which we've named hSDH5," he said.
"Previous genetic studies have shown that the hereditary paragangliomas PGL1, PGL3, and PGL4 are associated with mutations causing loss of SDH activity. Although the gene for PGL2 had not been identified, we knew that it was located on the same chromosome as the hSDH5 gene," he added.
Rutter and his colleagues sequenced the hSDH5 gene in three individuals with PGL2.
Of the 45 individuals within the affected lineage who inherited the mutation, 33 have developed PGL2, providing strong evidence that hSDH5 is the PGL2 gene.
The researchers suggest that identification of hSDH5 as the PGL2 gene has potential clinical implications for patients with familial PGL syndromes.
The study appears in journal Science.