Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline.

BACKGROUND

Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the REN (renin)-angiotensin system. Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms.

METHODS

Exome sequencing for a gene panel associated with renal disease was performed. The REN-angiotensin system was assessed by comprehensive biochemical analysis in blood. REN expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project.

RESULTS

The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the

CONCLUSIONS

Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the renin-angiotensin system in a patient with