title: Novel large deletion in AVPR2 gene causing copy number variation in a patient with X-linked nephrogenic diabetes insipidus.
abstract: BACKGROUND
  The diagnosis of cranial and nephrogenic diabetes insipidus (DI) can be clinically challenging. The application of molecular genetic analysis can help in resolving diagnostic difficulties.
  
  
  METHODS
  A 3 month-old boy presented with recurrent polyuria was admitted to Intensive Care Unit and was treated as DI. The patient also had a strong family history of polyuria affecting his maternal uncles. Molecular genetic analysis using Single Nucleotide Polymorphism (SNP) array detected a large deletion located at Xq28 region and the breakpoint was identified using PCR and Sanger sequencing. An 11,535 bp novel deletion affecting the entire APVR2 gene and the last intron and exon of the ARHGAP4 gene was confirmed. This large deletion is likely due to the 7-bp microhomology sequence at the junctions of both 5' and 3' breakpoints. No disease-causing mutation was identified for AQP2.
  
  
  CONCLUSIONS
  We report a novel deletion in a Chinese patient with congenital nephrogenic DI. We suggested that patients with suspected congenital DI should undergo genetic analysis of AVPR2 and AQP2 genes. A definitive diagnosis can benefit patient by treatment of hydrochlorothiazide and amiloride and avoiding unnecessary investigations.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China.
authors.forename: Chun Yiu
authors.initials: CY
authors.lastname: Law
authors.affiliation: Department of Paediatrics and Adolescent Medicine, United Christian Hospital, Hong Kong, China.
authors.forename: Kwok Leung
authors.initials: KL
authors.lastname: Ng
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
authors.forename: Ching Wan
authors.initials: CW
authors.lastname: Lam
mesh_terms: D056915:DNA Copy Number Variations; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D017483:Receptors, Vasopressin / Q000235:genetics*
chemical_list: C585768:AVPR2 protein, human; D017483:Receptors, Vasopressin
keywords: AVPR2; Novel deletion; X-linked nephrogenic diabetes insipidus