title: Novel mutations underlying nephrogenic diabetes insipidus in Arab families.
abstract: OBJECTIVE
  Nephrogenic Diabetes Insipidus (NDI) is genetically heterogeneous and may be inherited in an X-linked or autosomal recessive manner. We aimed to investigate the molecular basis of NDI among Arab families.
  
  
  METHODS
  Direct sequencing of coding regions for AQP2 and AVPR2 was used to identify underlying mutations. One large deletion required Southern blot analysis and a PCR-based strategy to identify deletion junctions.
  
  
  RESULTS
  We identified two novel missense mutations (AQP2:p.Gly100Arg and p.Gly180Ser) in AQP2 and one novel missense mutation (AVPR2:p.Gly122Asp), one previously reported missense mutation (AVPR2:p.Arg137His) and one novel contiguous deletion (AVPR2:c.25 + 273_ARHGAP4o:2650-420del) affecting AVPR2. We also describe evidence of lyonization associated with the novel deletion.
  
  
  CONCLUSIONS
  Two novel mutations were identified in each of AVPR2 and AQP2 underlying CNDI in Arab families. Identification of these mutations will facilitate early diagnosis of CNDI, counseling of families and provide opportunities for early intervention aimed at reducing morbidity. The presence of affected females and consanguinity, as is often observed in Arab communities should not be used to rule out AVPR2 as a candidate when considering diagnostic testing. Careful observation of phenotypic heterogeneity should be used in referring such families for both AQP2 and AVPR2 molecular genetic testing.
authors.affiliation: Aragene Laboratory, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Carroll
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Mojalli
authors.forename: Abbas
authors.initials: A
authors.lastname: Al-Abbad
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Hassoun
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Hamed
authors.forename: Rana
authors.initials: R
authors.lastname: Al-Amr
authors.forename: Abdul Islam
authors.initials: AI
authors.lastname: Butt
authors.forename: Brian Francis
authors.initials: BF
authors.lastname: Meyer
mesh_terms: D051399:Aquaporin 2 / Q000097:blood / Q000235:genetics*; D018912:Arabs / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017483:Receptors, Vasopressin / Q000097:blood / Q000235:genetics*; D012529:Saudi Arabia
chemical_list: C496023:AQP2 protein, human; D051399:Aquaporin 2; D017483:Receptors, Vasopressin