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 II 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 non-familial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%) familial and two of 37 ( approximately 5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX134 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both non-familial 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 ( approximately 3%) non-familial cases. P131R and M71fsX80 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 approximately 8% 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.
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 II 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 paragangliomapatients 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 non-familial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%) familial and two of 37 ( approximately 5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX134 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both non-familial 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 ( approximately 3%) non-familial cases. P131R and M71fsX80 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 approximately 8% of non-familial cases. These results also suggest that the commonness of the SDHDP81L mutation in North America is the result of both a founder effect and recurrent mutations.
Authors: B E Baysal; R E Ferrell; J E Willett-Brozick; E C Lawrence; D Myssiorek; A Bosch; A van der Mey; P E Taschner; W S Rubinstein; E N Myers; C W Richard; C J Cornelisse; P Devilee; B Devlin Journal: Science Date: 2000-02-04 Impact factor: 47.728
Authors: D Astuti; F Latif; A Dallol; P L Dahia; F Douglas; E George; F Sköldberg; E S Husebye; C Eng; E R Maher Journal: Am J Hum Genet Date: 2001-06-12 Impact factor: 11.025
Authors: P E Taschner; J C Jansen; B E Baysal; A Bosch; E H Rosenberg; A H Bröcker-Vriends; A G van Der Mey; G J van Ommen; C J Cornelisse; P Devilee Journal: Genes Chromosomes Cancer Date: 2001-07 Impact factor: 5.006
Authors: R F Badenhop; S Cherian; R S Lord; B E Baysal; P E Taschner; P R Schofield Journal: Genes Chromosomes Cancer Date: 2001-07 Impact factor: 5.006
Authors: S Niemann; J Becker-Follmann; G Nürnberg; F Rüschendorf; N Sieweke; M Hügens-Penzel; H Traupe; T F Wienker; A Reis; U Müller Journal: Am J Med Genet Date: 2001-01-01
Authors: Li-shar Huang; Gang Sun; David Cobessi; Andy C Wang; John T Shen; Eric Y Tung; Vernon E Anderson; Edward A Berry Journal: J Biol Chem Date: 2005-12-21 Impact factor: 5.157
Authors: Kathryn S King; Clara C Chen; Dimitrios K Alexopoulos; Millie A Whatley; James C Reynolds; Nicholas Patronas; Alexander Ling; Karen T Adams; Paraskevi Xekouki; Howard Lando; Constantine A Stratakis; Karel Pacak Journal: J Clin Endocrinol Metab Date: 2011-07-13 Impact factor: 5.958
Authors: Ivana Jochmanova; April Melody T Abcede; Ruby Jane S Guerrero; Chandy Lou P Malong; Robert Wesley; Thanh Huynh; Melissa K Gonzales; Katherine I Wolf; Abhishek Jha; Marianne Knue; Tamara Prodanov; Naris Nilubol; Leilani B Mercado-Asis; Constantine A Stratakis; Karel Pacak Journal: J Cancer Res Clin Oncol Date: 2020-02-15 Impact factor: 4.553
Authors: Sakari Vanharanta; Mary Buchta; Sarah R McWhinney; Sanna K Virta; Mariola Peçzkowska; Carl D Morrison; Rainer Lehtonen; Andrzej Januszewicz; Heikki Järvinen; Matti Juhola; Jukka-Pekka Mecklin; Eero Pukkala; Riitta Herva; Maija Kiuru; Nina N Nupponen; Lauri A Aaltonen; Hartmut P H Neumann; Charis Eng Journal: Am J Hum Genet Date: 2003-12-18 Impact factor: 11.025