title: A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL.
abstract: More than 40% of patients with paragangliomas (PGLs) harbor a germline mutation of the known PGL susceptibility genes, mainly in the SDHB or SDHD genes.
  
  
  
  The objective of the study was to characterize the genetic background of the French Canadian (FC) patients with PGLs and provide new clinical and paraclinical insights on SDHC-related PGLs.
  
  
  
  Genetic testing has been offered to FC patients affected with PGLs followed up at the adrenal genetics clinic at Centre hospitalier de l'Université de Montréal. After genetic counseling, 29 FC patients consented for PGL genetic testing.
  
  
  
  Thirteen of 29 patients (44.8%) carried a germline mutation. The same heterozygous nonsense mutation at codon 133 of exon 5 of the SDHC gene (c.397C>T, p.[Arg133Ter]) was found in nine patients, representing 69.2% of the patients having a germline mutation. Seventy percent of these patients had head and neck PGLs. Twenty percent had multiple and 30% had malignant PGLs. We traced back the ascending genealogy of 10 index cases (nine patients from our cohort and one patient referred to us) and found that this mutation was most probably introduced in Nouvelle France by a couple of French settlers who established themselves in the 17th century.
  
  
  
  We found that 31% of the PGLs in the French Canadian can be explained by the SDHC mutation (c.397C>T, p.[Arg133Ter]). The dominance of the SDHC mutation is unique to the FCs and is most likely due to a French founder effect. SDHC gene analysis should be prioritized in FC patients with PGL.
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourdeau
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Solange
authors.initials: S
authors.lastname: Grunenwald
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Khalifa
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Dumas
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Binet
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Nolet
authors.affiliation: Divisions of Endocrinology (I.B., S.G.) and Genetics (I.B., N.D., M.-C.B.), Department of Medicine, and Department of Pathology (S.N.), Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada H2W 1T8; Assistance Publique-Hôpitaux de Paris (N.B., E.K., A.-P.G.-R.), Service de Génétique, Hôpital Européen Georges Pompidou, F-75015 Paris, France; Université Paris Descartes (N.B., E.K., G.-R.), Faculté de Médecine, Sorbonne Paris Cité, F-75006 Paris, France; and INSERM (N.B., E.K., G.-R.), Unité Mixte de Recherche 970, Centre de Recherche de l'Hôpital Européen Georges Pompidou, F-75015 Paris, France.
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada / Q000208:ethnology; D005260:Female; D005602:France / Q000208:ethnology; D006258:Head and Neck Neoplasms / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human