Rei Hirose1, Yuya Tsurutani2, Chiho Sugisawa1, Kosuke Inoue1,3, Sachiko Suematsu1, Maki Nagata4, Naoki Hasegawa5, Yukio Kakuta5, Masato Yonamine6, Kazuhiro Takekoshi6, Noriko Kimura7, Jun Saito1, Tetsuo Nishikawa1. 1. Endocrinology and Diabetes Center, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kouhoku-ku, Yokohama, Kanagawa, 222-0036, Japan. 2. Endocrinology and Diabetes Center, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kouhoku-ku, Yokohama, Kanagawa, 222-0036, Japan. yuya97tsuru1055@gmail.com. 3. Department of Epidemiology, UCLA Fielding School of Public Health, 650 Charles E. Young Dr. South, 16-035 Center for Health Sciences, Los Angeles, CA, USA. 4. Department of Urology, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kouhoku-ku, Yokohama, Kanagawa, 222-0036, Japan. 5. Department of Pathology, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kouhoku-ku, Yokohama, Kanagawa, 222-0036, Japan. 6. Laboratory of Laboratory/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan. 7. Department of Diagnostic Pathology, National Hospital Organization Hakodate Hospital, 18-16 Kawahara-cho, Hakodate, Hokkaido, 041-8512, Japan.
Abstract
BACKGROUND: Pheochromocytoma and paraganglioma caused by succinate dehydrogenase gene mutations is called hereditary pheochromocytoma/paraganglioma syndrome. In particular, succinate dehydrogenase subunit B mutations are important because they are strongly associated with the malignant behavior of pheochromocytoma and paraganglioma . This is a case report of a family of hereditary pheochromocytoma/paraganglioma syndrome carrying a novel mutation in succinate dehydrogenase subunit B. CASE PRESENTATION: A 19-year-old Japanese woman, whose father died of metastatic paraganglioma, was diagnosed with abdominal paraganglioma, and underwent total resection. Succinate dehydrogenase subunit B genetic testing detected a splice-site mutation, c.424-2delA, in her germline and paraganglioma tissue. Afterwards, the same succinate dehydrogenase subunit B mutation was detected in her father's paraganglioma tissues. In silico analysis predicted the mutation as "disease causing." She is under close follow-up, and no recurrence or metastasis has been observed for 4 years since surgery. CONCLUSIONS: We detected a novel succinate dehydrogenase subunit B mutation, c.424-2delA, in a Japanese family afflicted with hereditary pheochromocytoma/paraganglioma syndrome and found the mutation to be responsible for hereditary pheochromocytoma/paraganglioma syndrome. This case emphasizes the importance of performing genetic testing for patients with pheochromocytoma and paraganglioma suspected of harboring the succinate dehydrogenase subunit B mutation (that is, metastatic, extra-adrenal, multiple, early onset, and family history of pheochromocytoma and paraganglioma) and offer surveillance screening to mutation carriers.
BACKGROUND:Pheochromocytoma and paraganglioma caused by succinate dehydrogenase gene mutations is called hereditary pheochromocytoma/paraganglioma syndrome. In particular, succinate dehydrogenase subunit B mutations are important because they are strongly associated with the malignant behavior of pheochromocytoma and paraganglioma . This is a case report of a family of hereditary pheochromocytoma/paraganglioma syndrome carrying a novel mutation in succinate dehydrogenase subunit B. CASE PRESENTATION: A 19-year-old Japanese woman, whose father died of metastatic paraganglioma, was diagnosed with abdominal paraganglioma, and underwent total resection. Succinate dehydrogenase subunit B genetic testing detected a splice-site mutation, c.424-2delA, in her germline and paraganglioma tissue. Afterwards, the same succinate dehydrogenase subunit B mutation was detected in her father's paraganglioma tissues. In silico analysis predicted the mutation as "disease causing." She is under close follow-up, and no recurrence or metastasis has been observed for 4 years since surgery. CONCLUSIONS: We detected a novel succinate dehydrogenase subunit B mutation, c.424-2delA, in a Japanese family afflicted with hereditary pheochromocytoma/paraganglioma syndrome and found the mutation to be responsible for hereditary pheochromocytoma/paraganglioma syndrome. This case emphasizes the importance of performing genetic testing for patients with pheochromocytoma and paraganglioma suspected of harboring the succinate dehydrogenase subunit B mutation (that is, metastatic, extra-adrenal, multiple, early onset, and family history of pheochromocytoma and paraganglioma) and offer surveillance screening to mutation carriers.
Authors: A Muth; J Crona; O Gimm; A Elmgren; K Filipsson; M Stenmark Askmalm; J Sandstedt; M Tengvar; E Tham Journal: J Intern Med Date: 2019-01-15 Impact factor: 8.989