title: A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.
abstract: X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.
authors.affiliation: Department of Biology, Faculty of Science, Hacettepe University, Beytepe, Ankara, 06800, Turkey.
authors.forename: Emel
authors.initials: E
authors.lastname: Saglar
authors.forename: Ferhat
authors.initials: F
authors.lastname: Deniz
authors.forename: Beril
authors.initials: B
authors.lastname: Erdem
authors.forename: Tugce
authors.initials: T
authors.lastname: Karaduman
authors.forename: Arif
authors.initials: A
authors.lastname: Yönem
authors.forename: Eylem
authors.initials: E
authors.lastname: Cagiltay
authors.forename: Hatice
authors.initials: H
authors.lastname: Mergen
mesh_terms: D019295:Computational Biology; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D008297:Male; D008958:Models, Molecular; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017483:Receptors, Vasopressin / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
chemical_list: C585768:AVPR2 protein, human; D017483:Receptors, Vasopressin; D004247:DNA
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