Horm Metab Res 2012; 44(05): 334-338
DOI: 10.1055/s-0032-1306308
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Screening of Mutations in Genes that Predispose to Hereditary Paragangliomas and Pheochromocytomas

S. Lefebvre
1   Hospices Civils de Lyon, Hôpital E. Herriot, Génétique moléculaire et clinique, 5 place d’Arsonval, Lyon, France
,
F. Borson-Chazot
2   Hospices Civils de Lyon, Endocrinologie, Groupement Hospitalier Est, Bron, France
,
N. Boutry-Kryza
1   Hospices Civils de Lyon, Hôpital E. Herriot, Génétique moléculaire et clinique, 5 place d’Arsonval, Lyon, France
,
N. Wion
3   CHU de Grenoble, Endocrinologie, Hôpital A. Michalon, Grenoble, France
,
F. Schillo
4   CHU de Besançon, Endocrinologie, Hôpital J. Minjoz, Besançon, France
,
J.-L. Peix
5   Hospices Civils de Lyon, Chirurgie digestive et endocrinienne, Centre hospitalier Lyon Sud, Pierre Bénite, France
,
L. Brunaud
6   CHU de Nancy, Chirurgie générale et endocrinienne, Hôpitaux de Brabois, Vandoeuvre, France
,
A. Finat
1   Hospices Civils de Lyon, Hôpital E. Herriot, Génétique moléculaire et clinique, 5 place d’Arsonval, Lyon, France
,
A. Calender
1   Hospices Civils de Lyon, Hôpital E. Herriot, Génétique moléculaire et clinique, 5 place d’Arsonval, Lyon, France
,
S. Giraud
1   Hospices Civils de Lyon, Hôpital E. Herriot, Génétique moléculaire et clinique, 5 place d’Arsonval, Lyon, France
› Author Affiliations
Further Information

Publication History

received 31 October 2011

accepted 16 February 2012

Publication Date:
19 April 2012 (online)

Abstract

Thirty per cent of the paragangliomas and pheochromocytomas reported are hereditary. Mutations in SDHB, SDHC, SDHD, and more recently SDHAF2 and TMEM127 genes have been described in these hereditary tumors. We looked for mutations in these 5 genes in a series of 269 patients with paragangliomas and/or pheochromocytomas. The SDHB, SDHC, and SDHD genes were analyzed in a series of 269 unrelated index patients with paragangliomas and/or pheochromocytomas using dHPLC screening of point mutations followed by direct sequencing and Multiplex PCR Liquid Chromatography to detect large rearrangements confirmed by quantitative PCR. In a second phase, we adapted Multiplex PCR Liquid Chromatography to the SDHAF2 and TMEM127 genes. This method and direct sequencing were applied to 230 patients without the SDHB, C, D mutations. Of the 269 patients, 44 carried a mutation (16.3%). Thirty-seven different mutations were identified: 18 in SDHB (including 2 large deletions), 8 in SDHD, 6 in SDHC, 5 in TMEM127, and no mutations in SDHAF2. Thirteen mutations have not been published so far. An exhaustive study of the different genes is needed to make possible a familial genetic diagnosis in paraganglioma and pheochromocytoma hereditary syndromes. Although mutations in SDHC and TMEM127 are less frequent than mutations in SDHB and SDHD, they also have less evident clinical feature indicators. Analyzing SDHAF2 must be restricted to familial extra-adrenal paragangliomas. Multiplex PCR Liquid Chromatography is a sensitive, fast, and inexpensive method for screening large rearrangements, which are infrequent in these syndromes.

 
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