Neurohypophyseal Diabetes Insipidus (NDI) via the AVP Gene

Neurohypophyseal Diabetes Insipidus (NDI) (OMIM# 125700), also called Central Diabetes Insipidus, is a neuroendocrine disorder resulting from deficiency of the antidiuretic hormone (ADH), also called arginine vasopressin, a hormone with the primary function of regulating the kidneys to retain water balance. NDI is characterized by polyuria and polydipsia. Patients may also show dehydration, vomiting, constipation, fever and development delay (Di Lorgi et al. Horm Res Paediatr 77(2):69-84, 2012).

The AVP gene (OMIM# 192340) encodes the antidiuretic hormone arginine vasopressin (AVP), which is synthesized in the hypothalamus of brain. It binds to the vasopressin type 2 receptor (V2R) in the collecting ducts of the kidney and activates a series of reactions to regulate transepithelium water permeability in renal collecting tubes, which increases water reabsorption from urine and maintains the body’s water homeostasis (Babey et al. Nature Review Endocrinology 7:701-714, 2011). Mutations in AVP mainly cause autosomal dominant NDI, however, a few mutations have been documented in families with an autosomal recessive form NDI. To date, approximately 70 mutations in AVP have been identified; the majority of them are missense mutations, although truncating mutations caused by nonsense, small insertions and deletions, and one large deletion including part of the AVP gene have been reported (Human Gene Mutation Database; Christensen et al. Clin Genet 83:44-52, 2013).

Analytical sensitivity may be high because all AVP mutations reported to date are expected to be detected by direct sequencing of genomic DNA. Clinical sensitivity is difficult to estimate due to the lack of documented cases.

To date, only one large deletion including part of the AVP gene has been reported (Human Gene Mutation Database; Christensen et al. Clin Genet 2013 83(1):44-52, 2013).

This test involves bidirectional Sanger sequencing of all coding exons and splice sites of the AVP gene. The full coding sequence of each exon plus ~10 bp of flanking DNA on either side are sequenced. We will also sequence any single exon (Test #100) in family members of patients with a known pathogenic variant or to confirm research results.