ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2019 and some content may be unavailable. To unlock all content for 2019, please visit the archives.

Abstract: SA-PO359

A Novel Aquaporin 2 Insertion Mutation in a Chinese Family with Autosomal Dominant Nephrogenic Diabetes Insipidus and Chronic Renal Failure

Session Information

Category: Trainee Case Report

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Tsai, Ping-Huang, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • Cheng, Chih-Jen, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • Lin, Shih-Hua P., Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Introduction

Mutations in aquaporin 2 (AQP2) cause mostly autosomal recessive or rarely autosomal dominant nephrogenic diabetes insipidus (NDI). Patients with autosomal dominant NDI usually exhibit less phenotype and have mutations in the carboxyl-terminal tail important intracellular routing of the AQP2. We described a family of autosomal dominant NDI carried a novel AQP2 mutation but presented a severe phenotype, which led to early-onset renal failure.

Case Description

A 26-year-old Chinese female manifested polyuria, polydipsia, and nocturia after birth. Her family history was non-revealing. She did not have non-obstructive hydronephrosis and never received NSAID or thiazide to treat her polyuria. Pertinent laboratory investigations showed abnormal renal function with serum creatinine 3.4 mg/dL, and hyperchloremic metabolic acidosis (chloride 115, HCO3- 19 mmol/L), persistently low urine osmolality (around 50-100 mOsm/kg.H2O) and markedly increased serum von Willebrand factor and coagulation factor VIII in response to desamino-8-D-arginine AVP (DDAVP) test. Direct sequencing of AVPR2 and AQP2 gene showed two nucleotide GC insertion at c.755 of AQP2, resulting in a frameshift mutation (p.R253Dfs*82, +52 AA) and altering the amino acid sequence between R254 to A271. Of note, her one-year-old son also exhibited severe polyuria two days after birth and was found carrying the same mutation.

Discussion

We presented the first autosomal dominant NDI family with a severe phenotype, including early-onset polyuria in the neonatal period and renal failure in early adulthood. The functional experiment focusing on autosomal dominant AQP2 mutations in the C-terminal end is warranted.