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Identical germline mutations in the TMEM 127 gene in two unrelated J apanese patients with bilateral pheochromocytoma
Author(s) -
Takeichi Naomi,
Midorikawa Sanae,
Watanabe Atsushi,
Naing Banyar Than,
Tamura Hideki,
WakakuriKano Toshiko,
Ishizaki Akira,
Sugihara Hitoshi,
Nissato Sumiko,
Saito Yuria,
Aita Yuichi,
Ishii Kiyoaki,
Igarashi Takehito,
Kawakami Yasushi,
Hara Hisato,
Ikeda Tatsuhiko,
Shimizu Kazuo,
Suzuki Shinichi,
Shimano Hitoshi,
Kawamoto Masashi,
Shimada Takashi,
Watanabe Tsuyoshi,
Oikawa Shinichi,
Takekoshi Kazuhiro
Publication year - 2012
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2012.04421.x
Subject(s) - sdhd , loss of heterozygosity , pheochromocytoma , sdhb , germline mutation , germline , medicine , endocrinology , biology , paraganglioma , mutation , multiple endocrine neoplasia type 2 , cancer research , genetics , gene , pathology , allele
Summary Objective Recently, TMEM 127 was shown to be a new pheochromocytoma susceptibility gene; this is consistent with its function as a tumour suppressor gene ( Journal of Clinical Endocrinology and Metabolism , 2009, 94 , 2817). Most pheochromocytomas arise from the adrenal medulla, and in approximately half of the cases, the tumours are bilateral ( Journal of Clinical Endocrinology and Metabolism , 2009, 94 , 2817; Journal of the American Medical Association , 2004, 292 , 943; Human Mutation , 2010, 31 , 41; Science , 2009, 325 , 1139). The aim of the present study was to determine whether TMEM 127 mutations are involved in the pathogenesis of pheochromocytomas/paragangliomas in Japanese subjects. Patients and Methods For this study, 74 unrelated patients with pheochromocytoma/paraganglioma who tested negative for mutations and deletions in RET , VHL , SDHB and SDHD were recruited through a multi‐institutional collaborative effort in Japan. The TMEM 127 gene sequence was determined in their germline DNA , and tumour DNA was analysed for the loss of heterozygosity. In addition, their TMEM 127 gene sequences were compared with sequences from 114 normal healthy, ethnically matched controls. Results Among the 74 eligible patients, two unrelated patients (2·7%) with bilateral adrenal pheochromocytoma were found to have an identical germline TMEM 127 mutation (c.116_119delTGTC, p.Ile41ArgfsX39) associated with 2q deletion loss of heterozygosity, which was also previously described in a Brazilian case ( Journal of the American Medical Association , 2004, 292 , 943). We also determined that none of the 114 normal healthy controls had this deletion mutation. Conclusion This is the first report showing that TMEM 127 mutation plays a pathological role in pheochromocytoma in an A sian population. Although our surveillance is limited, the prevalence and the phenotype of this gene mutation appear to be similar to those reported in previous studies.