Clinical and molecular characterization of a family with a dominant renin gene mutation and response to treatment with fludrocortisone

BACKGROUND: A family was identified with autosomal dominant inheritance of anemia, polyuria, hyperuricemia, and chronic kidney disease. Mutational analysis revealed a novel heterozygous mutation c.58T > C resulting in the amino acid substitution of cysteine for arginine in the preprorenin signal...

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Hauptverfasser: Bleyer, Anthony J. (VerfasserIn) , Zivná, M. (VerfasserIn) , Hulková, H. (VerfasserIn) , Hodanová, K. (VerfasserIn) , Vyletal, P. (VerfasserIn) , Sikora, J. (VerfasserIn) , Zivný, J. (VerfasserIn) , Sovová, J. (VerfasserIn) , Hart, T. C. (VerfasserIn) , Adams, J. N. (VerfasserIn) , Elleder, M. (VerfasserIn) , Kapp, Katharina (VerfasserIn) , Haws, R. (VerfasserIn) , Cornell, L. D. (VerfasserIn) , Kmoch, S. (VerfasserIn) , Hart, P. S. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2010 December
In: International journal of radiation oncology, biology, physics
Year: 2010, Jahrgang: 74, Heft: 6, Pages: 411-422
ISSN:1879-355X
Online-Zugang: Volltext
Verfasserangaben:A.J. Bleyer, M. Zivná, H. Hulková, K. Hodanová, P. Vyletal, J. Sikora, J. Zivný, J. Sovová, T.C. Hart, J.N. Adams, M. Elleder, K. Kapp, R. Haws, L.D. Cornell, S. Kmoch, and P.S. Hart

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245 1 0 |a Clinical and molecular characterization of a family with a dominant renin gene mutation and response to treatment with fludrocortisone  |c A.J. Bleyer, M. Zivná, H. Hulková, K. Hodanová, P. Vyletal, J. Sikora, J. Zivný, J. Sovová, T.C. Hart, J.N. Adams, M. Elleder, K. Kapp, R. Haws, L.D. Cornell, S. Kmoch, and P.S. Hart 
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520 |a BACKGROUND: A family was identified with autosomal dominant inheritance of anemia, polyuria, hyperuricemia, and chronic kidney disease. Mutational analysis revealed a novel heterozygous mutation c.58T > C resulting in the amino acid substitution of cysteine for arginine in the preprorenin signal sequence (p.cys20Arg) occurring in all affected members. - METHODS: Effects of the identified mutation were characterized using in vitro and in vivo studies. Affected individuals were clinically characterized before and after administration of fludrocortisone. - RESULTS: The mutation affects endoplasmic reticulum co-translational translocation and posttranslational processing, resulting in massive accumulation of non-glycosylated preprorenin in the cytoplasm. This affects expression of intra-renal RAS components and leads to ultrastructural damage of the kidney. Affected individuals suffered from anemia, hyperuricemia, decreased urinary concentrating ability, and progressive chronic kidney disease. Treatment with fludrocortisone in an affected 10-year-old child resulted in an increase in blood pressure and estimated glomerular filtration rate. - CONCLUSIONS: A novel REN gene mutation resulted in an alteration in the amino acid sequence of the renin signal sequence and caused childhood anemia, polyuria, and kidney disease. Treatment with fludrocortisone improved renal function in an affected child. Nephrologists should consider REN mutational analysis in families with autosomal dominant inheritance of chronic kidney disease, especially if they suffer from anemia, hyperuricemia, and polyuria in childhood. 
650 4 |a Adult 
650 4 |a Amino Acid Sequence 
650 4 |a Anemia 
650 4 |a Base Sequence 
650 4 |a Biopsy 
650 4 |a Blood Pressure 
650 4 |a Cell Line 
650 4 |a Child 
650 4 |a Chronic Disease 
650 4 |a Chymosin 
650 4 |a Cytoplasm 
650 4 |a DNA Mutational Analysis 
650 4 |a Endoplasmic Reticulum 
650 4 |a Enzyme Precursors 
650 4 |a Female 
650 4 |a Fludrocortisone 
650 4 |a Genes, Dominant 
650 4 |a Genetic Predisposition to Disease 
650 4 |a Glomerular Filtration Rate 
650 4 |a Glycosylation 
650 4 |a Heterozygote 
650 4 |a Humans 
650 4 |a Hyperuricemia 
650 4 |a Hypoaldosteronism 
650 4 |a Kidney Concentrating Ability 
650 4 |a Kidney Diseases 
650 4 |a Male 
650 4 |a Molecular Sequence Data 
650 4 |a Mutation 
650 4 |a Pedigree 
650 4 |a Phenotype 
650 4 |a Polyuria 
650 4 |a Protein Processing, Post-Translational 
650 4 |a Protein Sorting Signals 
650 4 |a Protein Transport 
650 4 |a Renin 
650 4 |a Transfection 
650 4 |a Treatment Outcome 
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700 1 |a Sikora, J.  |e VerfasserIn  |4 aut 
700 1 |a Zivný, J.  |e VerfasserIn  |4 aut 
700 1 |a Sovová, J.  |e VerfasserIn  |4 aut 
700 1 |a Hart, T. C.  |e VerfasserIn  |4 aut 
700 1 |a Adams, J. N.  |e VerfasserIn  |4 aut 
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700 1 |a Haws, R.  |e VerfasserIn  |4 aut 
700 1 |a Cornell, L. D.  |e VerfasserIn  |4 aut 
700 1 |a Kmoch, S.  |e VerfasserIn  |4 aut 
700 1 |a Hart, P. S.  |e VerfasserIn  |4 aut 
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