The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.
The Journal of Clinical Endocrinology & Metabolism. 2009-08-01; 94(8): 2817-2827
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1. J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27. doi: 10.1210/jc.2008-2504. Epub
2009 May 19.
The succinate dehydrogenase genetic testing in a large prospective series of
patients with paragangliomas.
Burnichon N(1), Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P,
Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat
J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo
AP; PGL.NET network.
Collaborators: Janand-Delenne B, Topolonski-Duyme H, Rodien P, Besson JL,
Penfornis A, Goizet C, Tabarin A, Hamon B, Francannet C, Bozorg Grayeli A,
Sterkers O, Abbouy C, Ajzenberg C, Goudet P, Faivre L, Chabre O, Schmerber S,
Carnaille B, Cardot-Bauters C, Wemeau JL, Vaneecloo FM, Borson-Chazot F, Giraud
S, Pignat JC, Peix JL, Lavieille JP, Zanaret M, Eisinger F, Pujol P, Ribstein J,
Makeieff M, Drui D, Bordure P, David A, Sadoul JL, Bobin S, Lepajolec C, Richard
S, Young J, Chanson P, Bertagna X, Libe R, Carel JC, Zennaty D, Brasnu D, Bonfils
P, Hans S, Zinzindohoue F, Tran Ba Huy P, El Bakkouri W, Cornélis F, Salomon R,
Niaudet P, Gilbert B, Klossek JM, Ricco JB, Kraimps JL, Delemer B, Guilhem I,
Odent S, Cailleux AF, Kuhn JM, Lefèvre H, Schlienger JL, Caron O, Dollfus H,
Lazard D, Fraysse B, Calvas P, Amar J, Duly-Bouhanick B, Battiston T, Caron P,
Robier A, Beutter P, Bressac de Paillerets B, Baudin E, Lumbroso J.
(1)Département de Génétique, Hôpital Européen Georges Pompidou, 20-40 rue
Leblanc, Paris, France.
CONTEXT: Germline mutations in SDHx genes cause hereditary paraganglioma.
OBJECTIVE: The aim of the study was to assess the indications for succinate
dehydrogenase (SDH) genetic testing in a prospective study.
DESIGN: A total of 445 patients with head and neck and/or thoracic-abdominal or
pelvic paragangliomas were recruited over 5 yr in 20 referral centers. In
addition to classical direct sequencing of the SDHB, SDHC, and SDHD genes, two
methods for detecting large genomic deletions or duplications were used,
quantitative multiplex PCR of short fluorescent fragments (QMPSF) and multiplex
ligation-dependent probe amplification (MLPA).
RESULTS: A large variety of SDH germline mutations were found by direct
sequencing in 220 patients and by QMPSF and MLPA in 22 patients (9.1%): 130 in
SDHD, 96 in SDHB, and 16 in SDHC. Mutation carriers were younger and more
frequently had multiple or malignant paraganglioma than patients without
mutations. A head and neck paraganglioma was present in 97.7% of the SDHD and
87.5% of the SDHC mutation carriers, but in only 42.7% of the SDHB carriers. A
thoracic-abdominal or pelvic location was present in 63.5% of the SDHB, 16.1% of
the SDHD, and in 12.5% of the SDHC mutation carriers. Multiple paragangliomas
were diagnosed in 66.9% of the SDHD mutation carriers. A malignant paraganglioma
was documented in 37.5% of the SDHB, 3.1% of the SDHD, and none of the SDHC
CONCLUSIONS: SDH genetic testing, including tests for large genomic deletions, is
indicated in all patients with head and neck and/or thoracic-abdominal or pelvic
paraganglioma and can be targeted according to clinical criteria.
PMID: 19454582 [Indexed for MEDLINE]