Pauline Romanet1, Amira Mohamed2, Sophie Giraud3, Marie-Françoise Odou4, Marie-Odile North5, Morgane Pertuit2, Eric Pasmant5, Lucie Coppin6, Céline Guien7, Alain Calender3, Françoise Borson-Chazot8, Christophe Béroud9, Pierre Goudet10,11, Anne Barlier1. 1. Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology, Hospital La Conception, Marseille, France. 2. Laboratory of Molecular Biology, Hospital La Conception, APHM, Marseille, France. 3. Genetics Department, Hospices Civils de Lyon, University Hospital (HCL), East Pathology Center, Lyon, Bron Cedex, France. 4. Service de Biochimie et Biologie Moléculaire "Hormonologie, Métabolisme-Nutrition, Oncologie", Centre de Biologie Pathologie, Centre Hospitalier Universitaire Lille, Lille Cedex, France. 5. Service de Génétique et Biochimie Moléculaires, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France. 6. Univ. Lille, INSERM, CHU Lille, UMR-S 1172, - JPARC - Jean-Pierre Aubert Research Center, Lille, France. 7. Aix Marseille Univ, APHM, INSERM, MMG, U 1251 Bioinformatic Team, Marseille, France. 8. Hospices Civils de Lyon, Fédération d'Endocrinologie, Université Claude Bernard Lyon 1, HESPER EA 7425, Lyon, France. 9. Aix Marseille Univ, APHM, INSERM, MMG, Department of Genetics, Hospital La Timone Enfants, Marseille, France. 10. Department of Endocrine Surgery, University Hospital of Dijon, and INSERM, U866, Dijon, France. 11. Epidemiology and Clinical Research in Digestive Oncology Team, and INSERM, CIC1432, Clinical Epidemiology Unit, University Hospital of Dijon, Clinical Investigation Center, Clinical Epidemiology/Clinical Trials Unit, Dijon, France.
Abstract
Context: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the MEN1 gene characterized by a broad spectrum of clinical manifestations, of which the most frequent are primary hyperparathyroidism, pituitary adenomas, and neuroendocrine tumors. Objective: The aim of this work was to facilitate interpretation of variants and improve the genetic counseling and medical care of families of patients with MEN1. Design, Setting, and Patients: The TENGEN network (Oncogenetics Network of Neuroendocrine Tumors) has interpreted and collected all allelic variants and clinical characteristics of the MEN1-positive patients identified through genetic testing performed in the French population from 1997 to 2015. Patients and their variants were registered in the locus-specific UMD-MEN1 database (www.umd.be/MEN1/). Main Outcomes: Variant classification, age-related penetrance, and odds ratios. Results: A total of 370 distinct variants reported in 1676 patients, including 181 unpublished variants, have been registered. This database analysis revealed a low frequency (6.6%) of benign or likely benign missense variants in MEN1. Eight families (1.9%) had members with familial isolated hyperparathyroidism and harbored the same mutations as that found in families with authentic MEN1. An association existed between large rearrangements and an earlier onset of the disease, whereas no difference was observed between truncating and nontruncating variants. Conclusion: The UMD-MEN1 database provides an exhaustive overview of the MEN1 variants present in the French population. For each variant, a classification is publicly available. Clinical data collections allow the determination of genotype-phenotype correlation and age-related penetrance of lesions in the cohort.
Context:Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the MEN1 gene characterized by a broad spectrum of clinical manifestations, of which the most frequent are primary hyperparathyroidism, pituitary adenomas, and neuroendocrine tumors. Objective: The aim of this work was to facilitate interpretation of variants and improve the genetic counseling and medical care of families of patients with MEN1. Design, Setting, and Patients: The TENGEN network (Oncogenetics Network of Neuroendocrine Tumors) has interpreted and collected all allelic variants and clinical characteristics of the MEN1-positive patients identified through genetic testing performed in the French population from 1997 to 2015. Patients and their variants were registered in the locus-specific UMD-MEN1 database (www.umd.be/MEN1/). Main Outcomes: Variant classification, age-related penetrance, and odds ratios. Results: A total of 370 distinct variants reported in 1676 patients, including 181 unpublished variants, have been registered. This database analysis revealed a low frequency (6.6%) of benign or likely benign missense variants in MEN1. Eight families (1.9%) had members with familial isolated hyperparathyroidism and harbored the same mutations as that found in families with authentic MEN1. An association existed between large rearrangements and an earlier onset of the disease, whereas no difference was observed between truncating and nontruncating variants. Conclusion: The UMD-MEN1 database provides an exhaustive overview of the MEN1 variants present in the French population. For each variant, a classification is publicly available. Clinical data collections allow the determination of genotype-phenotype correlation and age-related penetrance of lesions in the cohort.
Authors: R M Ruggeri; E Benevento; F De Cicco; B Fazzalari; E Guadagno; I Hasballa; M G Tarsitano; A M Isidori; A Colao; A Faggiano Journal: J Endocrinol Invest Date: 2022-08-30 Impact factor: 5.467
Authors: Carolina R C Pieterman; Samuel M Hyde; Si-Yuan Wu; Jace P Landry; Yi-Ju Chiang; Ioannis Christakis; Elizabeth G Grubbs; Sarah B Fisher; Paul H Graham; Steven G Waguespack; Nancy D Perrier Journal: Surgery Date: 2020-07-20 Impact factor: 3.982
Authors: Maria Luisa Brandi; Sunita K Agarwal; Nancy D Perrier; Kate E Lines; Gerlof D Valk; Rajesh V Thakker Journal: Endocr Rev Date: 2021-03-15 Impact factor: 19.871