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Abstract: TH-PO740

Whole Exome Sequencing Reveals Mutations in the Purinergic Receptors P2RX2 and P2RX7 as Novel Causes of Neurogenic Bladder and CKD

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic


  • Mann, Nina, Boston Children's Hospital, Boston, Massachusetts, United States
  • Kause, Franziska, Boston Children's Hospital, Boston, Massachusetts, United States
  • Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States
  • Connaughton, Dervla M., Boston Children's Hospital, Boston, Massachusetts, United States
  • Dai, Rufeng, Boston Children's Hospital, Boston, Massachusetts, United States
  • Kolvenbach, Caroline M., Harvard Medical School, Boston, Massachusetts, United States
  • Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Neurogenic bladder is caused by disruption of the normal neural pathways that regulate bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, recurrent urinary tract infections, and even chronic kidney disease and renal failure. Animal models of bladder dysfunction suggest that neurogenic bladder can be caused by single gene mutations. However, to date, no mutations have been identified in humans.


To identify monogenic causes of neurogenic bladder, we applied homozygosity mapping with whole exome sequencing (WES) to our worldwide cohort of families with congenital anomalies of the kidneys and urinary tract (CAKUT).


We identified a homozygous missense mutation (p.Gly322Arg) in the gene P2RX2 and a compound heterozygous missense mutation (p.Leu320Pro, p.Pro582Leu) in the gene P2RX7 in two families with neurogenic bladder. Both families also have secondary vesicoureteral reflux and chronic kidney disease. The mutations identified are well-conserved evolutionarily, rare in the general population, and have deleterious in silico prediction scores. P2RX2 and P2RX7 belong to the purinergic family of receptors, which are ATP-gated cation channels, and both are expressed in the urothelium and bladder smooth muscle. Additionally, P2rx2 knockout mice have impaired bladder reflexes (Cockayne J Physiol 567:621, 2005), which mimics the phenotype of our patients.


We identified recessive missense mutations in two purinergic receptors, P2RX2 and P2RX7, in families with neurogenic bladder. Purinergic signaling has been reported to play an important role in bladder contractility, and we therefore propose that mutations in these genes may be novel monogenic causes of neurogenic bladder in humans.


  • NIDDK Support