A Novel Somatic Deletion Mutation of ATP2B3 in Aldosterone-Producing Adenoma.
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.
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Masanori
M
Murakami
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. tyoshimoto.mem@tmd.ac.jp.
Takanobu
http://orcid.org/0000-0001-8002-4843
T
Yoshimoto
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Isao
I
Minami
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Ryotaro
R
Bouchi
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Kyoichiro
K
Tsuchiya
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.|Department of Preemptive Medicine and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Koshi
K
Hashimoto
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.|Center for Medical Welfare and Liaison Services, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Hajime
H
Izumiyama
Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Yasuhisa
Y
Fujii
Department of Pathology, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Takashi
T
Endo
Department of Pathology, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Takumi
T
Akashi
Department of Urology, Tachikawa Hospital, Tokyo, 190-0022, Japan.|Department of Biochemistry, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
Koshiro
K
Nishimoto
Department of Biochemistry, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
Kuniaki
K
Mukai
Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Kazunori
K
Kihara
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Yoshihiro
Y
Ogawa
D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000601:surgery; D000315:Adrenalectomy; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000601:surgery; D000450:Aldosterone / Q000378:metabolism*; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism*; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D017384:Sequence Deletion
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human
ATP2B3; Aldosterone-producing adenoma; CYP11B2; Primary aldosteronism