Abstract
Gitelman’s syndrome is an autosomal recessive disorder marked by salt wasting and hypokalaemia resulting from loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter. Gitelman’s syndrome is usually distinguished from Bartter’s syndrome by the presence of both hypomagnesaemia and hypocalciuria. Although recent advances in molecular genetics may make it possible to both diagnose and differentiate these diseases, the phenotypes sometimes overlap. Here we report two sporadic cases of Gitelman’s syndrome and two novel genotypes of SLC12A3. Patient 1 was a compound heterozygote with a known missense mutation, L849H, and a novel mutation, R852H in exon 22. Patient 2 was homozygous for the missense mutation L849H. To our knowledge, this is the first report of a patient homozygous for 849H. Interestingly, both patients were affected with autoimmune thyroid disease. Patient 1 was affected with Hashimoto’s disease, and Patient 2 was affected with Graves’ disease. The symptoms of Patient 2 were more serious than those of Patient 1. Although the patients both carried the 849H allele (Patient 1 as a heterozygote and Patient 2 as a homozygous), their clinical symptoms differed. The difference in the clinical features may have been due both to phenotypic differences and the fact that Gitelman’s syndrome is a complicated disorder.
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References
H.J. Gitelman, J.B. Graham, L.G. Welt, Trans. Assoc. Am. Physicians 79, 221–235 (1966)
M.A. Turman, Pediatr. Nephrol. 12, 23–25 (1998)
N. Jeck, M. Konrad, M. Peters, S. Weber, K.E. Bonzel, H.W. Seyberth, Pediatr. Res. 48, 754–758 (2000)
M. Konrad, M. Vollmer, H.H. Lemmink, L.P. van den Heuvel, N. Jeck, R. Vargas-Poussou et al., J. Am. Soc. Nephrol. 11, 1449–1459 (2000)
D.B. Simon, C. Nelson-Williams, M.J. Bia, D. Ellison, F.E. Karet, A.M. Molina et al., Nat. Genet. 12, 24–30 (1996)
S. Bhandari, J.H. Turney, Nephron 80, 373–379 (1998)
A. Bettineli, M.G. Bianchetti, E. Girardin, A. Caringella, M. Cecconi, A.C. Appiani et al., J. Pediatr. 120, 38–43 (1992)
N. Mastroianni, M. De Fusco, M. Zollo, G. Arrigo, O. Zuffardi, A. Bettinelli et al., Genomics 35, 486–493 (1996)
S. Kunchaparty, M. Palcso, J. Berkman, H. Velazquez, G.V. Desir, P. Bernstein et al., Am. J. Physiol. 277, 643–649 (1999)
H. Naraba, Y. Kokubo, H. Tomoike, N. Iwai, Hypertens. Res. 28, 805–809 (2005)
J.E. Jones, P.C. Desper, S.R. Shane, E.B. Flink, J. Clin. Invest. 45, 891–900 (1966)
C. McCaffrey, G.A. Quamme, Can. J. Comp. Med. 48, 51–57 (1984)
D.S. Munro, H. Renschler, G.M. Wilson, Metabolism 7, 124–132 (1958)
Medical Research Council, War Memorandum, 2nd edn rev. (London, Her Majesty’s Stat, 1943)
T. Nakayama, M. Soma, D. Rahmutula, Y. Ozawa, K. Kanmatsuse, Med. Sci. Monit. 7, 345–349 (2001)
T. Nakayama, M. Minato, M. Nakagawa, M. Soma, H. Tobe, N. Aoi et al., Endocrine 15, 277–282 (2001)
H.H. Lemmink, N.V. Knoers, L. Karolyi, H. van Dijk, P. Niaudet, C. Antignac et al., Kidney Int. 54, 720–730 (1998)
T. Monkawa, I. Kurihara, K. Kobayashi, M. Hayashi, T. Saruta, J. Am. Soc. Nephrol. 11, 65–70 (2000)
S. Fukuyama, S. Okudaira, S. Yamazato, M. Yamazato, T. Ohta, Kidney Int. 64, 808–816 (2003)
N. Maki, A. Komatsuda, H. Wakui, H. Ohtani, A. Kigawa, N. Aiba et al., Nephrol. Dial. Transplant. 19, 1761–1766 (2004)
S. Okinaka, K. Shizume, S. Iino et al., J. Clin. Endocrinol. Metab. 17, 1454–1459 (1957)
A.J. McFadzean, R. Yeung, Br. Med. J. 1, 451–455 (1967)
W.B. Schwartz, A.S. Relman, N. Engl. J. Med. 276, 383–389 (1967)
J.P. Tolins, M.K. Hostetter, T.H. Hostetter, J. Clin. Invest. 79, 1447–1458 (1987)
L. Bonfante, P.A. Davis, M. Spinello, A. Antonello, A. D’Angelo, A. Semplicini, L. Calo, Am. J. Kidney Dis. 38, 165–168 (2001)
S.H. Lin, J.C. Shiang, C.C. Huang, S.S. Yang, Y.J. Hsu, C.J. Cheng, J. Clin. Endocrinol. Metab. 90, 2500–2507 (2005)
K.P. Schlingmann, S. Weber, M. Peters, N. Niemann, V. Lene, K. Helga et al., Nat. Genet. 31, 166–170 (2002)
R.Y. Walder, D. Landau, P. Meyer, H. Shalev, M. Tsolia, Z. Borochowitz et al., Nat. Genet. 31, 171–174 (2002)
T. Nijenhuis, V. Vallon, A.W. van der Kemp, J. Loffing, J.G.J. Hoenderop, R.J.M. Bindels, J. Clin. Invest. 115, 1651–1658 (2005)
N. Tago, Y. Kokubo, N. Inamoto, H. Naraba, H. Tomoike, N. Iwai, Hypertens. Res. 27, 327–331 (2004)
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Aoi, N., Nakayama, T., Tahira, Y. et al. Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman’s syndrome. Endocr 31, 149–153 (2007). https://doi.org/10.1007/s12020-007-0024-9
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DOI: https://doi.org/10.1007/s12020-007-0024-9