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Preclinical diagnosis and identification of the chimeric CYP11B1/CYP11B2 gene in two pediatric cases of a Japanese family with glucocorticoid-remediable aldosteronism

Hypertension Research volume 44, pages 891–893 (2021)Cite this article

Glucocorticoid-remediable aldosteronism (GRA), also known as familial aldosteronism type 1, is a form of aldosteronism caused by unequal crossing over between the CYP11B1 gene, which encodes 11β-hydroxylase, and the CYP11B2 gene, which encodes aldosterone synthase (AS). Although GRA accounts for ~0.7% of primary aldosteronism cases worldwide [1], it is extremely rare in Japan, with only five cases in two pedigrees reported to date [2, 3]. GRA is inherited in an autosomal-dominant fashion and causes hypertension at an early age, with a high incidence of cerebrovascular complications at a young age [4].

We previously reported three cases of GRA in a Japanese family [2]. Nearly 20 years later, the proband has two sons. Here, the genetic diagnosis and identification of crossover sites of the chimeric gene in the descendants are described. When the proband was 21 years old, she, along with her sister and mother, was incidentally found to have familial hypertension [2]. Examination of the proband and her sister revealed hypokalemia and a high plasma aldosterone concentration (PAC) with suppressed plasma renin activity (PRA) in addition to adrenocorticotropin (ACTH)-dependent changes in PAC and suppression of PAC by dexamethasone. Genetic testing by long-range PCR revealed the CYP11B1/CYP11B2 chimeric gene in these three individuals, leading to the diagnosis of GRA. The proband was initially treated with dexamethasone and subsequently with a calcium-channel blocker. Over 20 years, she successfully delivered two boys while using hydralazine during pregnancy. A few years later, she requested genetic testing for GRA for her sons and visited our department. Both children, a 5-year-old and a 3-year-old, had a normal perinatal and developmental status and normal to slightly elevated blood pressure with normokalemia (4.0, 4.6 mEq/L) in addition to high PAC (348, 367 pg/mL) and reduced PRA (0.1, 0.3 ng/mL/h). Genetic testing for GRA was performed with permission after genetic counseling.

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Acknowledgements

We are very grateful to emeritus professor Toshio Ogura, Health Service Center of Okayama University, for providing previous medical information regarding the proband.

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Authors and Affiliations

  1. Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Yasuhiro Nakano, Nahoko Iwata & Fumio Otsuka

  2. Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Kanako Ogura-Ochi

  3. Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Kosei Hasegawa

  4. Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Akira Hirasawa

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  1. Yasuhiro Nakano
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Contributions

YN wrote the manuscript, NI performed the genetic testing, FO, KO, and KH examined the cases, AH provided the genetic consulting, and FO revised the manuscript. All authors contributed to the article.

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Correspondence to Fumio Otsuka.

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Nakano, Y., Iwata, N., Ogura-Ochi, K. et al. Preclinical diagnosis and identification of the chimeric CYP11B1/CYP11B2 gene in two pediatric cases of a Japanese family with glucocorticoid-remediable aldosteronism. Hypertens Res 44, 891–893 (2021). https://doi.org/10.1038/s41440-021-00633-1

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