Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas

Background: Paragangliomas are rare and highly heritable tumours of neuroectodermal origin that often develop in the head and neck region. Germline mutations in the mitochondrial complex 11 genes, SDHB, SDHC, and SDHD, cause hereditary paraganglioma (PGL). Methods: We assessed the frequency of SDHB, SDHC, and SDHD gene mutations by PCR amplification and sequencing in a set of head and neck paraganglioma patients who were previously managed in two otolaryngology clinics in the USA. Results: Fifty-five subjects were grouped into 10 families and 37 non-familial cases. Five of the nonfamilial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%). familial and two of 37 (similar to5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX1 34 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both nonfamilial cases had multiple tumours. P81L and R38X mutations have previously been reported in other PGL families and P81L was suggested as a founder mutation. Allelic analyses of different chromosomes carrying these mutations did not show common disease haplotypes, strongly suggesting that R38X and P81L are potentially recurrent mutations. Germline SDHB mutations were identified in two of 10 (20%) familial and one of 33 (similar to3%) non-familial cases. PI 31 R and M71 fsX80 were identified in the familial cases and Q59X was identified in the one non-familial case. The non-familial case had a solitary, tumour. No mutations could be identified in the SDHC gene in the remaining four families and 20 sporadic cases. Conclusions: Mutations in SDHD are the leading cause of head and neck paragangliomas in this clinic patient series. SDHD and SDHB mutations account for 70% of familial cases and similar to8% of non-familial cases. These results also suggest that the commonness of the SDHD P81L mutation in North. America is the result of both a founder effect and recurrent mutations.