Head-neck paragangliomas (HNPGL) are neural crest derived tumors. At variance with paragangliomas located in the abdomen and the chest which are generally catecholamine secreting (sPGL) and sympathetic in origin, they are, in fact, parasympathetic in origin and generally not secreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL , MAX and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH), clinical, laboratory (including metanephrines) and instrumental examinations, patients were divided into 3 groups: a) with a positive FH for HNPGL (index cases only); b) with a negative FH and multiple HNPGL (synchronous or metachronous) or HNPGL associated to a sPGL; c) with negative FH and single HNPGL. The 10 patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) all proved to be SDHD mutation carriers. Among the 53 patients in group c), 10 presented germ-line mutations (3 SDHB, 3 SDHD, 2 VHL, 2 SDHAF2). A sPGL was found at diagnosis or follow up in 5 patients (6,3%),,all of whom were SDHD mutation carriers. No SDHC, SDHA, MAX and TMEM127 mutations were found. In SDHD mutation carriers none of the patients affected by HNPGL associated with sPGL presented a missense mutations. In conclusion, a positive FH or the presence of multiple HNPGL are strong predictors for germ-line mutations, which are also present in 18,8% of patients carefully classified as sporadic. The most frequently mutated gene by far is SDHD but others, including SDHB, SDHAF2 and VHL, may be affected.

Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients

AMBROSIO, Maria Rosaria;ZATELLI, Maria Chiara;
2012

Abstract

Head-neck paragangliomas (HNPGL) are neural crest derived tumors. At variance with paragangliomas located in the abdomen and the chest which are generally catecholamine secreting (sPGL) and sympathetic in origin, they are, in fact, parasympathetic in origin and generally not secreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL , MAX and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH), clinical, laboratory (including metanephrines) and instrumental examinations, patients were divided into 3 groups: a) with a positive FH for HNPGL (index cases only); b) with a negative FH and multiple HNPGL (synchronous or metachronous) or HNPGL associated to a sPGL; c) with negative FH and single HNPGL. The 10 patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) all proved to be SDHD mutation carriers. Among the 53 patients in group c), 10 presented germ-line mutations (3 SDHB, 3 SDHD, 2 VHL, 2 SDHAF2). A sPGL was found at diagnosis or follow up in 5 patients (6,3%),,all of whom were SDHD mutation carriers. No SDHC, SDHA, MAX and TMEM127 mutations were found. In SDHD mutation carriers none of the patients affected by HNPGL associated with sPGL presented a missense mutations. In conclusion, a positive FH or the presence of multiple HNPGL are strong predictors for germ-line mutations, which are also present in 18,8% of patients carefully classified as sporadic. The most frequently mutated gene by far is SDHD but others, including SDHB, SDHAF2 and VHL, may be affected.
2012
Piccini, V.; Rapizzi, E.; Bacca, A.; Di Trapani, G.; Pulli, R.; Giachè, V.; Zampetti, B.; Lucci Cordisco, E.; Canu, L.; Corsini, E.; Faggiano, A.; Deiana, L.; Carrara, D.; Tantardini, V.; Mariotti, S.; Ambrosio, Maria Rosaria; Zatelli, Maria Chiara; Parenti, G.; Colao, A.; Pratesi, C.; Bernini, G.; Ercolino, T.; Mannelli, M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1605067
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