A novel AVPR2 missense mutation in a Chinese boy with severe inherited nephrogenic diabetes insipidus.J Pediatr Endocrinol Metab. 2011; 24(9-10):807-9.JP
Inherited nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to arginine vasopressin (AVP). The most common cause is mutations in the AVP receptor 2 (AVPR2) gene at Xq28. Severe complications of NDI are rare but can occur after severe dehydration without treatment. A 7-year-old boy presented with short stature and severe intellectual disability other than polyuria and polydipsia. The karyotype was normal. Direct sequencing revealed a novel missense mutation c.506T > C (p.L169P) in AVPR2 in the patient. His mother was heterozygous for the mutation. The mutation was absent in 103 unrelated healthy males and predicted to be consistently pathogenic by several prediction methods, including Polyphen, SIFT, PMut, PhD-SNP, SNPs3D, PANTHER, and MEMPACK. Awareness of the primary signs of NDI, polyuria, and polydipsia would facilitate early diagnosis and treatment to prevent its severe complications. Also, molecular analysis will provide a rapid and definitive diagnosis and facilitate genetic counseling for family planning.