Bi-allelic mutations in renin-angiotensin system genes, associated with renal tubular dysgenesis, can also present as a progressive chronic kidney disease
- 1 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Pediatric Nephrology
- Vol. 35 (6), 1125-1128
- https://doi.org/10.1007/s00467-020-04524-4
Abstract
Background Bi-allelic loss of function variations in genes encoding proteins of the renin-angiotensin system (AGT, ACE, REN, AGTR1) are associated with autosomal recessive renal tubular dysgenesis, a severe disease characterized by the absence of differentiated proximal tubules leading to fetal anuria and neonatal end-stage renal disease. Case-Diagnosis/Treatment We identified bi-allelic loss of function mutations in ACE, the gene encoding angiotensin-converting enzyme, in 3 unrelated cases displaying progressive chronic renal failure, whose DNAs had been sent for suspicion of juvenile hyperuricemic nephropathy, nephronophthisis, and cystic renal disease, respectively. In all cases, patients were affected with anemia whose severity was unexpected regarding the level of renal failure and with important polyuro-polydipsia. Conclusions Bi-allelic loss of function mutation of ACE can have atypical and sometimes late presentation with chronic renal failure, anemia (out of proportion with the level of renal failure), and polyuro-polydipsia. These data illustrate the usefulness of next generation sequencing and "agnostic" approaches to elucidate cases with chronic kidney disease of unknown etiology and to broaden the spectrum of phenotypes of monogenic renal diseases. It also raises the question of genetic modifiers involved in the variation of the phenotypes associated with these mutations.This publication has 16 references indexed in Scilit:
- Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary TractJournal of the American Society of Nephrology, 2017
- Renin-angiotensin system inhibitors linked to anemia: a systematic review and meta-analysisQJM: An International Journal of Medicine, 2015
- Renal tubular dysgenesisPediatric Nephrology, 2013
- Survival over 2 years of autosomal-recessive renal tubular dysgenesisClinical Kidney Journal, 2012
- Inherited renal tubular dysgenesis may not be universally fatalPediatric Nephrology, 2010
- Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney FailureAmerican Journal of Human Genetics, 2009
- A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutationsAmerican Journal of Medical Genetics Part A, 2006
- Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to OligohydramniosJournal of the American Society of Nephrology, 2006
- Erythropoietin deficiency in hyporeninemiaAmerican Journal of Kidney Diseases, 1999
- Possible new autosomal recessive syndrome with unusual renal histopathological changesAmerican Journal of Medical Genetics, 1983