Identification of a novel large deletion mutation in the AVPR2 gene responsible for hereditary nephrogenic diabetes insipidus in an infant: a case report.

BACKGROUND: Hereditary nephrogenic diabetes insipidus (HNDI) type1 is a rare genetic disorder that results from mutations in the AVPR2 gene, which encodes the arginine vasopressin receptor 2. The primary clinical manifestations of this disorder encompass polydipsia, polyuria and urine with low specific gravity. At present, there is no curative treatment, and the principal treatment goal is to manage symptoms in order to prevent complications such as dehydration, brain injury, and hydroureteronephrosis.

CASE DESCRIPTION: This case report presents a 7-month-old boy who presented with persistent low-grade fever that could not be explained by common infections, rheumatological and immunological diseases and other etiologies, resulting in difficulties in diagnosis and poor treatment outcomes. However, through a comprehensive review of the medical history and meticulous screening of laboratory tests, it was discovered that the child exhibited polyuria and low-specific-gravity urine, accompanied by a family history indicating polydipsia and polyuria. Following fluid replacement and oral administration of hydrochlorothiazide, the fever abated. Whole-exome sequencing disclosed a copy-number deletion of approximately 2.046 kb at Xq28, which entailed the deletion mutation of exons 3-4 of the haploinsufficient gene AVPR2. This was expected to lead to nonsense-mediated decay, and finally, the diagnosis of HNDI type1 was confirmed.

CONCLUSIONS: The primary clinical manifestation of this case is fever, which underscores the atypical symptoms of nephrogenic diabetes insipidus during infancy. It also emphasizes the necessity of considering the potential for dehydration fever caused by diabetes insipidus when diagnosing fever of unknown origin. Furthermore, in this case, the copy number variation of the AVPR2 gene was successfully identified via whole-exome sequencing technology. A novel large-fragment deletion mutation was discovered, which broadens the mutation spectrum of the AVPR2 gene and substantially enhances the diagnostic accuracy.