A founder SDHB mutation in Portuguese paraganglioma patients.

We would like to report a genetic screening of SDHB, SDHC, SDHD and SDHAF2 genes (hereafter abbreviated to SDHx) in patients with paragangliomas (PGL) and phaeochromocytomas (PCC) from northern Portugal. PGL and PCC are neuroendocrine tumours that can be caused by heterozygous germline loss-of-function mutations in SDHx genes (Gimenez-Roqueplo et al. 2012). The spectrum of germline SDHx mutations varies considerably among different countries, a circumstance that is related to the existence of several founder mutations. This is particularly marked in The Netherlands (Hensen et al. 2012), where six founder mutations were discovered, but evidence for founder effects was also observed for SDHx mutations in Austrian (Janecke et al. 2010), Italian (Simi et al. 2005) and Spanish (Cascon et al. 2009) populations. In addition to familial PGL or PCC, germline SDHx mutations have also been observed in patients without familial history of disease, sometimes classified as ‘occult’ familial cases (Lima et al. 2007). This phenomenon may be associated with the low penetrance of SDHx mutations, which is about 50%, although increasing in older individuals (Burnichon et al. 2009), and with the genomic imprinting observed in SDHD and SDHAF2 genes (Gimenez-Roqueplo et al. 2012). We report the genetic study of 37 individuals diagnosed with PGL or PCC between 2009 and 2012, of which three were familial cases and 34 were sporadic. Sporadic cases were defined as those having no familial history of PGL or PCC in the parental and grandparental generations and disease was considered to be inherited when at least two first-degree relatives or two seconddegree relatives were affected by these tumours. Only the index cases from familial PGLs were considered for all the analyses. Patients displaying syndromic features associated with VHL, MEN2 or NF1 were excluded from the study. Written informed consent for genetic testing was obtained from all patients. Themajority of patients developed PGL (27/37; 73.0%) and ten developed PCC (27.0%). The clinical and pathological features of the 37 patients are shown in Table 1.