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A Novel Somatic Deletion Mutation of ATP2B3 in Aldosterone-Producing Adenoma
Masanori Murakami1, Takanobu Yoshimoto2, Isao Minami1
1Department 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.
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.
Insights
Researchers discovered a new gene mutation, ATP2B3, in aldosterone-producing adenoma. This finding sheds light on the causes of primary aldosteronism and excess aldosterone production.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Aldosterone-producing adenoma (APA) causes primary aldosteronism (PA).
- Somatic mutations in genes like KCNJ5, ATP1A1, ATP2B3, and CACNA1D are implicated in APA pathogenesis.
Observation:
- A 62-year-old male patient with PA and a left adrenal mass underwent adrenalectomy.
- Immunohistochemistry confirmed strong aldosterone synthase (CYP11B2) expression in the tumor, characteristic of APA.
Findings:
- A novel somatic deletion mutation (c.1269_1274delTGTGCT) was identified in the ATP2B3 gene within the adrenal tumor.
- This mutation (p.Val424_Leu425del) is predicted to increase intracellular calcium levels, leading to elevated CYP11B2 expression and excess aldosterone.
Implications:
- The identified novel ATP2B3 mutation reinforces its role in APA development.
- This discovery contributes to understanding the molecular mechanisms driving excess aldosterone production in APA.
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