Autosomal dominant mutation in the signal peptide of renin in a kindred with anemia, hyperuricemia, and CKD

Bodo B. Beck, Howard Trachtman, Michael Gitman, Ilene Miller, John A. Sayer, Andrea Pannes, Anne Baasner, Friedhelm Hildebrandt, Matthias T F Wolf

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Homozygous or compound heterozygous mutations in renin (REN) cause renal tubular dysgenesis, which is characterized by death in utero due to kidney failure and pulmonary hypoplasia. The phenotype resembles the fetopathy caused by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker intake during pregnancy. Recently, heterozygous REN mutations were shown to result in early-onset hyperuricemia, anemia, and chronic kidney disease (CKD). To date, only 3 different heterozygous REN mutations have been published. We report mutation analysis of the REN gene in 39 kindreds with hyperuricemia and CKD who previously tested negative for mutations in the UMOD (uromodulin) and HNF1B (hepatocyte nuclear factor 1β) genes. We identified one kindred with a novel thymidine to cytosine mutation at position 28 in the REN complementary DNA, corresponding to a tryptophan to arginine substitution at amino acid 10, which is found within the signal sequence (c.28T>C; p.W10R). On this basis, we conclude that REN mutations are rare events in patients with CKD. Within the kindred, we found affected individuals over 4 generations who carried the novel REN mutation and were characterized by significant anemia, hyperuricemia, and CKD. Anemia was severe and disproportional to the degree of decreased kidney function. Because all heterozygous REN mutations that have been described are localized in the signal sequence, screening of the REN gene for patients with CKD with hyperuricemia and anemia may best be focused on sequencing of exon 1, which encodes the signal peptide.

Original languageEnglish (US)
Pages (from-to)821-825
Number of pages5
JournalAmerican Journal of Kidney Diseases
Volume58
Issue number5
DOIs
StatePublished - Nov 2011

Fingerprint

Hyperuricemia
Protein Sorting Signals
Chronic Renal Insufficiency
Renin
Anemia
Mutation
Hepatocyte Nuclear Factor 1
Uromodulin
Genes
Angiotensin Receptor Antagonists
Cytosine
Amino Acid Substitution
Angiotensin-Converting Enzyme Inhibitors
Tryptophan
Thymidine
Renal Insufficiency
Arginine
Exons
Complementary DNA
Phenotype

Keywords

  • chronic kidney disease
  • erythropoiesis
  • Renin
  • uromodulin associated kidney disease

ASJC Scopus subject areas

  • Nephrology

Cite this

Autosomal dominant mutation in the signal peptide of renin in a kindred with anemia, hyperuricemia, and CKD. / Beck, Bodo B.; Trachtman, Howard; Gitman, Michael; Miller, Ilene; Sayer, John A.; Pannes, Andrea; Baasner, Anne; Hildebrandt, Friedhelm; Wolf, Matthias T F.

In: American Journal of Kidney Diseases, Vol. 58, No. 5, 11.2011, p. 821-825.

Research output: Contribution to journalArticle

Beck, BB, Trachtman, H, Gitman, M, Miller, I, Sayer, JA, Pannes, A, Baasner, A, Hildebrandt, F & Wolf, MTF 2011, 'Autosomal dominant mutation in the signal peptide of renin in a kindred with anemia, hyperuricemia, and CKD', American Journal of Kidney Diseases, vol. 58, no. 5, pp. 821-825. https://doi.org/10.1053/j.ajkd.2011.06.029
Beck, Bodo B. ; Trachtman, Howard ; Gitman, Michael ; Miller, Ilene ; Sayer, John A. ; Pannes, Andrea ; Baasner, Anne ; Hildebrandt, Friedhelm ; Wolf, Matthias T F. / Autosomal dominant mutation in the signal peptide of renin in a kindred with anemia, hyperuricemia, and CKD. In: American Journal of Kidney Diseases. 2011 ; Vol. 58, No. 5. pp. 821-825.
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