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Bartter syndrome representing digenic-based salt-losing tubulopathies presumably accelerated by renal insufficiency

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Abstract

Bartter syndrome and Gitelman syndrome (GS) are autosomal recessive disorders usually caused by homozygous or compound heterozygous mutations in causative genes. In some patients, these two syndromes cannot be discriminated based on clinical features or mutation type; thus, a single disease concept, salt-losing tubulopathies (SLTs), has been used instead. Despite the existence of several SLT causative genes, cases of digenic heterozygous mutations in two different genes are extremely rare. Here, we report the case of a 36-year-old woman with renal insufficiency and hypokalemia caused by an SLT. To evaluate the SLT phenotype, we performed next-generation sequencing (NGS) with a gene panel including SLC12A3, SLC12A1, CLCNKB, and CLCNKA as well as laboratory examinations and diuretic loading tests. The results of the diuretic loading tests were consistent with a GS phenotype, while the NGS results showed that the patient had heterozygous mutations in SLC12A1 and CLCNKB. Both genes have been associated with BS, suggesting that the SLT was caused by digenic heterozygous mutations in two different genes. To date, only a few SLT cases caused by digenic heterozygous mutations in two different genes have been reported. The digenic SLT phenotype in the patient was presumably accelerated by moderate renal insufficiency.

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Authors and Affiliations

  1. Department of Nephrology, JCHO Isahaya General Hospital, Nagasaki, Japan

    Ryusuke Umene, Hideyuki Arai, Kazuki Matsumura & Yuka Ishimaru

  2. Department of Nephrology, Nagasaki University School of Medicine Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8102, Japan

    Ryusuke Umene, Mineaki Kitamura, Tadashi Uramatsu, Yoko Obata & Tomoya Nishino

  3. Ken-ai-kai Maeda Clinic, Nagasaki, Japan

    Kanenori Maeda

  4. Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Takayasu Mori, Eisei Sohara & Shinichi Uchida

Authors
  1. Ryusuke Umene
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  2. Mineaki Kitamura
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  3. Hideyuki Arai
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  4. Kazuki Matsumura
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  5. Yuka Ishimaru
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  6. Kanenori Maeda
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  7. Tadashi Uramatsu
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  8. Yoko Obata
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  9. Takayasu Mori
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  10. Eisei Sohara
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  11. Shinichi Uchida
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  12. Tomoya Nishino
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Corresponding author

Correspondence to Mineaki Kitamura.

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The authors have declared that no conflict of interest exists.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethical Committee of Isahaya General Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Written informed consent for genetic testing and publishing this report was obtained from the patient in accordance with the guidelines of the Ethical Committee of Isahaya General Hospital.

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Umene, R., Kitamura, M., Arai, H. et al. Bartter syndrome representing digenic-based salt-losing tubulopathies presumably accelerated by renal insufficiency. CEN Case Rep 9, 375–379 (2020). https://doi.org/10.1007/s13730-020-00489-3

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  • DOI: https://doi.org/10.1007/s13730-020-00489-3

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