Abstract
Aldosterone-producing adenoma (APA) is a form of primary aldosteronism (PA). Recent studies suggested that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes are involved in the pathogenesis of APA. We report a case of a 62-year-old man diagnosed as PA with left adrenal mass. He underwent adrenalectomy for treatment. We identified a novel somatic deletion mutation in ATP2B3 in the adrenal tumor: c.1269_1274delTGTGCT which spans three codons (423–425) resulting in p.Val424_Leu425del. Immunohistochemical analysis revealed strong expression of aldosterone synthase (CYP11B2) in the tumor tissue, which is consistent with APA. Here, we identified a novel somatic deletion mutation in ATP2B3, which results in the amino acid sequences increasing intracellular calcium concentrations as reported previously, leading to increased aldosterone synthase (CYP11B2) expression and following excess aldosterone production in the APA cells. The novel ATP2B3 mutation detected in our case supports the pathogenic significance of the locus spanning the codon 424–426 of ATP2B3.
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Acknowledgments
The authors thank the members of the Molecular Endocrinology and Metabolism, Tokyo Medical and Dental University. This research is partially supported by the “Advancing Care of Primary Aldosteronism in Japan Study”—Japan Primary Aldosteronism Study (JPAS)—from the Japan Agency for Medical Research and development, AMED. We thank Mr. Shinya Sasai in the Department of Pathology, Tachikawa Hospital, for great assistance of immunohistochemistry; Dr. Takeshi Yamazaki in the Graduate School of Integrated Arts and Sciences, Hiroshima University, for giving us rabbit antihuman 3βHSD and CYP17 antibodies; as well as Dr. Celso E. Gomez-Sanchez in the University of Mississippi Medical Center for giving us excellent mouse monoclonal antihuman CYP11B2 and rat monoclonal antihuman CYP11B1 antibodies.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of Tokyo Medical and Dental University research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Murakami, M., Yoshimoto, T., Minami, I. et al. A Novel Somatic Deletion Mutation of ATP2B3 in Aldosterone-Producing Adenoma. Endocr Pathol 26, 328–333 (2015). https://doi.org/10.1007/s12022-015-9400-9
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DOI: https://doi.org/10.1007/s12022-015-9400-9