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Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome


Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.

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This study was supported by a grant from the Ministry of Health, Labour and Welfare (Japan) for Research on Rare Intractable Diseases in the Kidney and Urinary Tract (H24-nanchitou (nan)-ippan-041 to Kazumoto Iijima) in the “Research on Measures for Intractable Diseases” Project and a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Subject ID: 15K09691 to KN and 26293203 to KI).

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Correspondence to Kandai Nozu.

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Matsunoshita, N., Nozu, K., Yoshikane, M. et al. Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome. J Hum Genet 63, 887–892 (2018).

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