Novel SLC12A1 (NKCC2) Mutations in Two Families with Bartter Syndrome Type 1

  • ADACHI Masanori
    Department of Endocrinology & Metabolism, Clinical Research Institute, Kanagawa Children's Medical Center
  • ASAKURA Yumi
    Department of Endocrinology & Metabolism, Clinical Research Institute, Kanagawa Children's Medical Center
  • SATO Yoshiaki
    Department of Neonatology, Kanagawa Children's Medical Center
  • TAJIMA Toshihiro
    Department of Pediatrics, Hokkaido University School of Medicine
  • NAKAJIMA Takeo
    Department of Neonatology, Sapporo City General Hospital
  • YAMAMOTO Toshiyuki
    International Research and Educational Institute for Integrated Medical Science, Tokyo Women's Medical University
  • FUJIEDA Kenji
    Department of Pediatrics, Asahikawa Medical College

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Abstract

Bartter syndrome (BS) type 1, also referred to antenatal BS, is a genetic tubulopathy with hypokalemic metabolic alkalosis and prenatal onset of polyuria leading to polyhydramnios. It has been shown that BS type 1 is caused by mutations in the SLC12A1 gene encoding bumetanide-sensitive Na-K-2Cl - cotransporter (NKCC2). We had the opportunity to care for two unrelated Japanese patients of BS type 1 with typical manifestations including polyhydramnios, prematurity, hypokalemia, alkalosis, and infantile-onset nephrocalcinosis. Analysis of the SLC12A1 gene demonstrated four novel mutations: N117X, G257S, D792fs and N984fs. N117X mutation is expected to abolish most of the NKCC2 protein, whereas G257, which is evolutionary conserved, resides in the third transmemebrane domain. The latter two frameshift mutations reside in the intra-cytoplasmic C-terminal domain, which illustrates the importance of this domain for the NKCC2 function. In conclusion, we found four novel SLC12A1 mutations in two BS type 1 patients. Development of effective therapy for hypercalciuria is mandatory to prevent nephrocalcinosis and resultant renal failure.<br>

Journal

  • Endocrine Journal

    Endocrine Journal 54 (6), 1003-1007, 2007

    The Japan Endocrine Society

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