Abstract
Congenital nephrogenic diabetes insipidus (CNDI) is a rare renal disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2). The clinical signs of CNDI include polyuria, compensatory polydipsia, dehydration, electrolyte disorder, and developmental retardation without prompt treatment. In this study we report a rare case of CNDI caused by a single base transition in AQP2 gene. A 4.5 years old male patient suffered from oral dryness, polydipsia, and polyuria for more than 3 years. Laboratory examinations showed hypernatremia, hyperchloremia, and decreased urine osmolality and specific gravity. Ultrasound and MRI found bilateral upper ureteral dilatation and hydronephrosis. Furthermore, sequencing analysis found a C>T transition leading to a T108M missense mutation of AQP2. The patient was given low sodium diet and treated with hydrochlorothiazide followed by amiloride with indomethacin. The patient's clinical course improved remarkably after 1 year of treatment. This study reports the first case of CNDI featuring T108M missense mutation alone. These findings demonstrate a causative role of T108M mutation for CNDI and contribute to the mechanistic understanding of CNDI disease process.