4.1.3. Complex II and Paragangliomas

Mutations in *SDHA*, *SDHB*, *SDHC*, *SDHD*, *SDHAF2*, and *SDHAF3* have been identified in an increasing number of neoplasms, mainly paragangliomas (rare neoplasms of the autonomic nervous system) and gastrointestinal stromal tumors. A discussion of these mutations is beyond the scope of this article but the topic has been extensively reviewed by others [38–43]. Variants in these genes have been associated with a high probability of developing cancer. To improve the identification of putative cancer-inducing human genetic variants, 22 known human variants of *SDHA* were examined in yeast [44]. Complementation tests of the homologous mutations in yeast *sdh1* identified 16 variants that affected the growth of yeast on the non-fermentable carbon source glycerol. The corresponding 16 human variants were proposed to be putative cancer inducing amino acid substitutions.


**Table 1.** Pathologies resulting from mutations in genes encoding Complex II subunits and assembly factors, and their yeast homologs.

<sup>1</sup> Paragangliomas were not included in the table. <sup>2</sup> The patient died at five months of age following a respiratory infection before developing other phenotypes. <sup>3</sup> In different patients.
