title: An unusual case of hereditary nephrogenic diabetes insipidus (HNDI) affecting mother and daughter.
abstract: Hereditary nephrogenic diabetes iInsipidus (HNDI) is an uncommon disorder due to a resistance to anti-diuretic hormone leading to a reduced urinary concentrating ability. The X-linked form is fully expressed in hemizygous male patients, but diabetes insipidus may also present in heterozygous females where it must be distinguished from autosomal and other secondary causes. We report a mother and daughter in the same family with HNDI due to a heterozygous deletion in exon 1 of the AVPR2 gene, not previously described in the literature. A 5-year-old girl was referred for investigation of polyuria and polydipsia. The patient had a water deprivation test elsewhere at the age of 3 that was inconclusive. A degree of water restriction was imposed leading to headaches. The thyroid, cortisol, renal, and calcium profiles were normal. Her mother showed similar symptoms that had not been previously investigated. AQP2 (Aquaporin) and initial AVPR2 gene sequencing had not identified a mutation, but subsequent quantitative polymerase chain reaction analysis revealed a heterozygous large exon 1 deletion of the AVPR2 gene. The same deletion was also found in the child's mother. The patient's symptoms have significantly improved on appropriate treatment. Further analysis revealed skewed X inactivation in mother and daughter.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Giri
authors.forename: Rachel
authors.initials: R
authors.lastname: Hart
authors.forename: Caroline
authors.initials: C
authors.lastname: Jones
authors.forename: Ian
authors.initials: I
authors.lastname: Ellis
authors.forename: Renuka
authors.initials: R
authors.lastname: Ramakrishnan
mesh_terms: D002675:Child, Preschool; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D009035:Mothers; D009679:Nuclear Family; D010375:Pedigree; D017483:Receptors, Vasopressin / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C585768:AVPR2 protein, human; D017483:Receptors, Vasopressin