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Paracellin-1 gene mutation with multiple congenital abnormalities

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Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive renal tubular disorder characterized by renal magnesium wasting, hypercalciuria, advanced nephrocalcinosis and progressive renal failure. Mutations in the paracellin-1 (CLDN16) gene have been defined as the underlying genetic defect. The tubular disorders and progression in renal failure are usually resistant to magnesium substitution and hydrochlorothiazide therapy, but hypomagnesemia may improve with advanced renal insufficiency. We present a patient with a homozygous truncating CLDN16 gene mutation (W237X) who had early onset of renal insufficiency despite early diagnosis at 2 months. He also had additional abnormalities including horseshoe kidney, neonatal teeth, atypical face, cardiac abnormalities including coarctation of the aorta associated with atrial and ventricular septal defects, umbilical hernia and hypertrichosis. To the best of our knowledge, this is the youngest case diagnosed as familial hypomagnesemia with hypercalciuria and nephrocalcinosis and the first case having such additional congenital abnormalities independent of the disease itself.

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  1. Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP (1999) Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285:103–106

    Article  CAS  Google Scholar 

  2. Blanchard A, Jeunemaitre X, Coudol P, Dechaux M, Froissart M, May A, Demontis R, Fournier A, Paillard M, Houillier P (2001) Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle. Kidney Int 59:2206–2215

    Article  CAS  Google Scholar 

  3. Weber S, Schneider L, Peters M, Misselwitz J, Ronnefarth G, Boswald M, Bonzel KE, Seeman T, Sulakova T, Kuwertz-Broking E, Gregoric A, Palcoux JB, Tasic V, Manz F, Scharer K, Seyberth HW, Konrad M (2001) Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 12:1872–1881

    CAS  PubMed  Google Scholar 

  4. Konrad M, Weber S (2003) Recent advances in molecular genetics of hereditary magnesium-losing disorders. J Am Soc Nephrol 14:249–260

    Article  Google Scholar 

  5. Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG (2000) Hypomagnesaemia-hypercalciuria-nephrocalcinosis: a report of nine cases and a review. Nephrol Dial Transplant 15:605–610

    Article  CAS  Google Scholar 

  6. Praga M, Vara J, Gonzalez-Parra E, Andres A, Alamo C, Araque A, Ortiz A, Rodicio JL (1995) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Kidney Int 47:1419–1425

    Article  CAS  Google Scholar 

  7. Michelis MF, Drash AL, Linarelli LG, De Rubertis FR, Davis BB (1972) Decreased bicarbonate threshold and renal magnesium wasting in a sibship with distal renal tubular acidosis: evaluation of the pathophysiological role of parathyroid hormone. Metabolism 21:905–920

    Article  CAS  Google Scholar 

  8. Nicholson JC, Jones CL, Powell HR, Walker RG, McCredie DA (1995) Familial hypomagnesemia-hypercalciuria leading to end-stage renal failure. Pediatr Nephrol 9:74–76

    Article  CAS  Google Scholar 

  9. Weber S, Hoffmann K, Jeck N, Saar K, Boeswald M, Kuwertz-Broeking E, Meij IIJ, Knoers NV, Cochat P, Sulakova T, Bonzel KE, Soergel M, Manz F, Schaerer K, Seyberth HW, Reis A, Konrad M (2000) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene. Eur J Hum Genet 8:414–422

    Article  CAS  Google Scholar 

  10. Kang JH, Choi HJ, Cho HY, Lee JH, Ha IS, Cheong HI, Choi Y (2005) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis associated with CLDN16 mutations. Pediatr Nephrol 20:1490–1493

    Article  Google Scholar 

  11. Alon US (1997) Nephrocalcinosis. Curr Opin Pediatr 9:160–165

    Article  CAS  Google Scholar 

  12. Tajima T, Nakae J, Fujieda K (2003) Two heterozygous mutations of CLDN16 in a Japanese patient with FHHNC. Pediatr Nephrol 18:1280–1282

    Article  Google Scholar 

  13. Tasic V, Dervisov D, Koceva S, Weber S, Konrad M (2005) Hypomagnesemia with hypercalciuria and nephrocalcinosis: case report and a family study. Pediatr Nephrol 20:1003–1006

    Article  Google Scholar 

  14. Wang TH, Johnston K, Hsieh CL, Dennery PA (1994) Terminal deletion of the long arm of chromosome 2 in a premature infant with karyotype: 46,XY,del(2)(q37). Am J Med Genet 49:399–401

    Article  CAS  Google Scholar 

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Correspondence to Salih Kavukçu.

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Türkmen, M., Kasap, B., Soylu, A. et al. Paracellin-1 gene mutation with multiple congenital abnormalities. Pediatr Nephrol 21, 1776–1778 (2006).

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