The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.
BACKGROUND
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.


METHODS
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 mutation carriers.


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.
Burnichon
Nelly
N
Département de Génétique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, Paris, France.
Rohmer
Vincent
V
Amar
Laurence
L
Herman
Philippe
P
Leboulleux
Sophie
S
Darrouzet
Vincent
V
Niccoli
Patricia
P
Gaillard
Dominique
D
Chabrier
Gérard
G
Chabolle
Frédéric
F
Coupier
Isabelle
I
Thieblot
Philippe
P
Lecomte
Pierre
P
Bertherat
Jérôme
J
Wion-Barbot
Nelly
N
Murat
Arnaud
A
Venisse
Annabelle
A
Plouin
Pierre-François
PF
Jeunemaitre
Xavier
X
Gimenez-Roqueplo
Anne-Paule
AP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000201:enzymology / Q000235:genetics*; D011446:Prospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*
D013385:Succinate Dehydrogenase