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Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1

Nature Genetics volume 12, pages 248–253 (1996)Cite this article

Abstract

Autosomal recessive pseudohypoaldosteronism type I is a rare life-threatening disease characterized by severe neonatal salt wasting, hyperkalaemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormones. Investigation of affected offspring of consanguineous union reveals mutations in either the α or β subunits of the amiloride-sensitive epithelial sodium channel in five kindreds. These mutations are homozygous in affected subjects, co-segregate with the disease, and introduce frameshift, premature termination or missense mutations that result in loss of channel activity. These findings demonstrate the molecular basis and explain the pathophysiology of this disease

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References

  1. Cheek, D. & Perry, J.W. A salt wasting syndrome in infancy. Arch. Dis. Childh. 33, 252–256 (1958).

    Article  CAS  Google Scholar 

  2. Dillon, M.J. et al. Pseudohypoaldosteronism. Arch. Dis. Childh. 55, 427–434 (1980).

    Article  CAS  Google Scholar 

  3. Popow, C., Pollak, A., Herkner, K., Scheibenreiter, S. & Swoboda, W. Familial pseudohypoaldosteronism. Acta Paediat. Scand. 77, 136–141 (1988).

    Article  CAS  Google Scholar 

  4. Speiser, P.W., Stoner, E. & New, M.I. Pseudohypoaldosteronism: a review and report of two new cases. In Mechanisms and clinical aspects of steroid hormone resistance. (eds Chrousos, G.R, Loriaux, D.T. & Lipsett, M.B.) 173–195 (Plenum Press, New York, 1986).

    Chapter  Google Scholar 

  5. Donnell, G.N., Litman, N. & Roldan, M., Am. J. Dis. Child. 97, 813–828 (1959).

    Article  CAS  Google Scholar 

  6. Mathew, P.M., Manasra, K.B. & Hamdan, J.A. Indomethacin and cation-exchange resin in the management of pseudohypoaldosteronism. Clinical Pediat. 1, 58–60 (1993).

    Article  Google Scholar 

  7. Hanukoglu, A. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. J.Clin. Endocrinn. Metab. 73, 936–944 (1991).

    Article  CAS  Google Scholar 

  8. Hanukoglu, A., Bistritzer, T., Rakover, V. & Mandelberg, A. Pseudohypoaldosteronism with increased sweat and saliva electrolyte values and frequent lower respiratory tract infections mimicking cyctic fibrosis. J.Pediat. 125, 752–755 (1994).

    Article  CAS  Google Scholar 

  9. Hogg, R.J., Marks, J.F., Marver, D. & Frolich, J.C. Long term observations in a patient with pseudohypoaldosteronism. Pediat. Nephrology. 5, 205–210 (1991).

    Article  CAS  Google Scholar 

  10. Limal, J.M., Rapport, R., Dechaux, M., Riffaud, C. & Morin, C. Familial dominant pseudohypoaldosteronism. Lancet. 1, 51 (1978).

    Article  CAS  Google Scholar 

  11. Hanukoglu, A., Fried, D. & Gotlieb, A. Inheritance of pseudohypoaldosteronism. Lancet. 1, 1359 (1978).

    Article  CAS  Google Scholar 

  12. Rösier, A. The natural history of salt-wasting disorders of adrenal and renal origin. J. Clin. Endocrin. Metab. 59, 689–700 (1984).

    Article  Google Scholar 

  13. Armanini, D. et al. Aldosterone-receptor deficiency in pseudohypoaldosteronism. New Engl. J. Med. 313, 1178–1181 (1985).

    Article  CAS  Google Scholar 

  14. Kuhnle, U. et al. Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects. J. CIin. Endocrin. Metab. 70, 638–641 (1990).

    Article  CAS  Google Scholar 

  15. Bosson, D. et al. Generalized unresponsiveness to mineralocorticoid hormones: familial recessive pseudohypoaldosteronism due to aldosterone-receptor deficiency. Acta Endocrin. 113, S376–S381 (1986).

    Article  Google Scholar 

  16. Komesaroff, P.A., Verity, K. & Fuller, P.J. Pseudohypoaldosteronism: molecular characterization of the mineralocorticoid receptor. J. CIin. Endocrin. & Metab. 79, 27–31 (1994).

    CAS  Google Scholar 

  17. Zennaro, M.C., Borensztein, R., Jeunemaitre, X., Armanini, D. & Soubrier, F. No alteration in the primary structure of the mineralocorticoid receptor in a family with pseudohypoaldosteronism. J.CIin. Endocrin. Metab. 79, 32–38 (1994).

    CAS  Google Scholar 

  18. Horisberger, J.D., Canessa, C. & Rossier, B.C., Palmer, L.G. The epitheliall sodium channel-recent developments. Cell Physiol. Biochem. 32, 283–294 (1993).

    Article  Google Scholar 

  19. Rossier, B.C. & Palmer, L.G. Mechanism of aldosterone action on sodium and potassiium transport. In The Kidney, physiology and pathophysiology, (eds Seldin, D.W. & Giebisch, G.) 1373–1409 (Raven Press, New York, 1992).

    Google Scholar 

  20. Canessa, C.M., Horisberger, J.D. & Rossier, B.D. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature. 361, 467–470 (1993).

    Article  CAS  Google Scholar 

  21. Canessa, C.M. et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 367, 463–467 (1994).

    Article  CAS  Google Scholar 

  22. Shimkets, R.A. et al. Liddle's Syndrome: heritable human hypertension caused by mutation in the B subunit of the epithelial sodium channel. Cell. 79, 407–414 (1994).

    Article  CAS  Google Scholar 

  23. Hansson, J.H. et al. Hypertension caused by a truncated epithelial sodium channel subunit: genetic heterogeneity of Liddle's syndrome. Nature Genet. 11, 76–82 (1995).

    Article  CAS  Google Scholar 

  24. Hansson, J.H. et al. Adenovo missense mutation of the B subunit of the epithelial sodium channel causes hypertension and Liddle's syndrome, identifying a proline-rich segment critical for regulation of channel activity. Proc. Natl. Acad. Sci. USA 92, 11495–11499 (1995).

    Article  CAS  Google Scholar 

  25. Schild, L. et al. A mutation in the epithelial sodium channel causing Liddle's disease increases channel activity in the Xenopus laevis oocyte expression system. Proc. Natl. Acad. Sci. USA 92, 5699–5703 (1995).

    Article  CAS  Google Scholar 

  26. Lander, E.S. & Botstein, D. Homozygosity mapping: A way to map human recessive traits with the DNA of inbred children. Science 236, 1567–1570 (1987).

    Article  CAS  Google Scholar 

  27. Gyapay, G. et al. The 1993–94 Genethon human genetic linkage map. Nature Genet. 7, 246–339 (1994).

    Article  CAS  Google Scholar 

  28. Li, X.J., Xu, R.H., Guggino, W.B. & Snyder, S.H. Alternatively spliced forms of the alpha subunit of the epithelial sodium channel: distinct sites for amiloride binding and channel pores. Mol. Pharmacol. 47, 1133–1140 (1995).

    CAS  PubMed  Google Scholar 

  29. McDonald, F.J., Snyder, P.M., McCaray, P.B. Jr. & Welsh, M.J. Cloning, expression, and tissue distrubution of a human amiloride-sensitive Na+ channel. Am. J. Physiol. 268, L728–734 (1994).

    Google Scholar 

  30. McDonald, F.J., Price, M.P., Snyder, P.M. & Welsh, M.J. Cloning and expression of the β and γ subunits of the human epithelial sodium channel. Am. J. Physiol. 268, C1157–C1163 (1995).

    Article  CAS  Google Scholar 

  31. Puoti, A. et al. The highly selective low-conductance epithelial Na channel of Xenopus laevis A6 kidney cells. Am J. Physiol 269, C188–C197 (1995).

    Article  CAS  Google Scholar 

  32. Waldmann, R., Champigny, G., Bassilana, F., Voilley, N. & Lazdunski, M. Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel. J. Biol. Chem. 270, 27411–27414 (1995).

    Article  CAS  Google Scholar 

  33. Huang, M. & Chalfie, M. Gene interactions affecting mechanosensory transduction in Caenomabditis elegans. Nature. 367, 467–470 (1994).

    Article  CAS  Google Scholar 

  34. Chalfie, M. & Wolinsky, E. The identification and suppression of inherited neurodegeneration in Caenomabditis elegans. Nature. 345, 410–416 (1990).

    Article  CAS  Google Scholar 

  35. Duc, C., Farman, N., Canessa, C.M., Bonvalet, J-P. & Rossier, B.C. Cell specific expression of epithelial sodium channel α, β and γ in aldosterone responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry. J. Cell. Biol. 127, 1907–1921 (1994).

    Article  CAS  Google Scholar 

  36. Strang, L.B. Fetal lung liquid: secretion and reabsorption. Physiol. Rev. 71, 991–1016 (1991).

    Article  CAS  Google Scholar 

  37. Hummler et al. Early death due to defective neonatal lung liquid clearance in alpha ENaC-deficient mice. Nature Genet. 12, 325–328 (1996).

    Article  CAS  Google Scholar 

  38. Simon, D. et al. Gittleman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive NaCl cotransporter. Nature Genet. 12, 24–30 (1996).

    Article  CAS  Google Scholar 

  39. Bell, G., Karam, J. & Rutter, W. Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc. Natl. Acad. Sci. USA 78, 5759–5763 (1981).

    Article  CAS  Google Scholar 

  40. Canessa, C.M., Merillat, A.M. & Rossier, B.C. Membrane topology of the epithelial sodium channel in intact cells. Am. J. Ped. 267, C1682–169 (1994).

    CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Genetics, Boyer Center for Molecular Medicine, New Haven, Connecticut, 06510, USA

    Sue S. Chang, Yin Lu, Richard A. Shimkets, Carol Nelson-Williams & Richard P. Lifton

  2. Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Sue S. Chang & Richard P. Lifton

  3. Institut de Pharmacologie et de Toxicologie, Universite de Lausanne, Rue du Bugnon 27, CH-1005, Lausanne, Switzerland

    Stefan Grunder, Laurent Schild & Bernard C. Rossier

  4. Department of Pediatrics, E. Wolfson Hospital, Holon

    Aaron Hanukoglu

  5. Tel-Aviv University, Sackler School of Medicine, Tel Aviv, Israel

    Aaron Hanukoglu

  6. Department of Endocrinology and Metabolism, The Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel

    Ariel Rösler

  7. Department of Pediatrics, Dhahran Health Center, Dhahran, Saudi Arabia

    P.M. Mathew

  8. Research Institute, College of Judea and Samaria, Ariel

    Israel Hanukoglu

  9. Institute of Endocrinology, Sourasky Medical Center, Tel-Aviv, Israel

    Israel Hanukoglu

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  1. Sue S. Chang
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Chang, S., Grunder, S., Hanukoglu, A. et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 12, 248–253 (1996). https://doi.org/10.1038/ng0396-248

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  • DOI: https://doi.org/10.1038/ng0396-248

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