Novel AQP2 Mutations and Clinical Characteristics in Seven Chinese Families With Congenital Nephrogenic Diabetes Insipidus

Abstract

ObjectiveMutations in AQP2 (aquaporin-2) lead to rare congenital nephrogenic diabetes insipidus (NDI), which has been limitedly studied in Chinese population.MethodsTwenty-five subjects from seven families with NDI in a department (Beijing, PUMCH) were screened for AQP2 mutations. Clinical characteristics were described and genotype-phenotype correlation analysis was performed.ResultsWe identified 9 AQP2 mutations in 13 patients with NDI, including 3 novel AQP2 mutations (p.G165D, p.Q255RfsTer72 and IVS3-3delC). Missense mutations were the most common mutation type, followed by splicing mutations, and frameshift mutations caused by small deletion or insertion. The onset-age in our patients was younger than 1 year old. Common manifestations included polydipsia, polyuria (7/7) and intermittent fever (6/7). Less common presentations included short stature (3/7) and mental impairment (1/7). High osmotic hypernatremia and low osmotic urine were the main biochemical features. Dilation of the urinary tract was a common complication of NDI (3/6). Level of serum sodium in NDI patients with compound het AQP2 mutations was higher than non-compound het mutations.ConclusionIn the first and largest case series of NDI caused by AQP2 mutation in Chinese population, we identified 9 AQP2 mutations, including 3 novel mutations. Phenotype was found to correlate with genotypes, revealed by higher level of serum sodium in patients with compound het AQP2 mutations than non-compound het mutations. This knowledge broadens genotypic and phenotypic spectrum for rare congenital NDI and provided basis for studying molecular biology of AQP2.

Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology

“…Although the molecular mechanisms of Liddle syndrome are well-studied and amiloride is used as an effective therapy against the significant hypertension that many patients suffer from, it has been found that not all patients respond the same way to this therapy which leaves them susceptible for hypertension-induced risks ( Pradervand et al, 1999 ). NDI is a more prevalent disease and novel mutations have been discovered recently ( Gao et al, 2020 ; Li et al, 2021 ). However, these studies suggest that some mechanisms of, e.g., AQP2 trafficking remain to be unveiled ( Olesen and Fenton, 2021 ).…”

Aquaporins: A new target for traditional Chinese medicine in the treatment of digestive system diseases

“…This leads to the insertion of AQP2 in the apical plasma membrane, which is responsible for water reabsorption ( Hj and Th, 2016 ; Ouyang et al, 2020 ). Dysregulation of AQP2 is closely associated with several clinical disorders characterized by disturbances in body water balance, including congenital nephrogenic diabetes insipidus ( Li Q. et al, 2021 ), lithium-induced nephrogenic diabetes insipidus, electrolyte disturbances, acute and chronic renal function failure, ureteral obstruction, nephrotic syndrome, congestive heart failure, and liver cirrhosis ( Kwon et al, 2013 ).…”

Exploring the diversity of AVPR2 in Primates and its evolutionary implications

“…Diabetes Insipidus, characterized by excessive water loss, is one of the best studied diseases in this context. Approximately 250 mutations in the AVPR2 gene have been found to explain nearly 90% of human Congenital Nephrogenic Diabetes Insipidus (cNDI), with the remaining 10% attributed to mutations in AQP2 ( Bichet and Bockenhauer, 2016 ; Peng et al, 2019 ; Li et al, 2021 ). As a result, collecting ducts do not reabsorb water as they should.…”