SDHB mutation analysis in familial and sporadic phaeochromocytoma identifies a novel mutation

Abstract

P haeochromocytoma is a rare, neuroendocrine, chromaffin staining tumour that usually arises within the adrenal medulla, although extra-adrenal phaeochromocytomas also appear in ganglia of the sympathetic nervous system. Approximately 10% of phaeochromocytomas are hereditary1 and may be found in association with von Hippel-Lindau dis ease, multiple endocrine neoplasia type 2, or neurofibromato sis type 1.1¿3 Familial paraganglioma (PGL) is a inherited dis order characterised by the development of highly vascular tumours in the head and neck. Recent studies have related the presence of mutations on structural (SDHC, SDHD) and cata lytic (SDHB) succinate dehydrogenase subunits to familial and sporadic phaeochromocytoma and/or paraganglioma sus ceptibility. While the SDHD locus is maternally imprinted, SDHB has classical autosomal dominant inheritance. Since Baysal et al4 first described SDHD mutations as being associated with PGL, the screening of such alterations has become routine in the diagnosis of paraganglioma and phaeochromocytoma.5 Astuti et al6 reported the first known mutations in the SDHB gene that caused susceptibility to familial phaeochromocytoma alone and to familial phaeo chromocytoma with head and neck paraganglioma. A recent study reported mutations in the SDHB gene in ¿20% cases of PGL and ¿3% of sporadic paragangliomas. With regard to SDHC, only one study has identified a germline SDHC mutation in all the affected members of a family as being the underlying cause of PGL3.8 To investigate further the involvement of SDHB and SDHC in paraganglioma and phaeochromocytoma susceptibility, we searched for germline mutations in 22 patients, 17 with phaeochromocytoma, three with paraganglioma, and two cases with both (table 1).