title: Identification of an NPHP1 deletion causing adult form of nephronophthisis.
abstract: OBJECTIVE
  Nephronophthisis (NPHP) is an autosomal recessive cystic disease of the kidney with main characteristic features of polyuria/polydipsia, mild or absent proteinuria, interstitial fibrosis, and tubular cysts. NPHP is responsible for 5-10 % of inheritable end-stage renal disease (ESRD) cases. We investigated the clinical features and genetic cause of NPHP in a Persian family with three siblings affected by tubulointerstitial nephropathy reaching ESRD in adulthood.
  
  
  METHODS
  Uromodulin (UMOD), known to be involved in adult medullary cystic kidney disease, and nephronophthisis 1 (NPHP1) were investigated in the genomic DNA of the probands using DNA sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis and molecular karyotyping.
  
  
  RESULTS
  No mutation was detected in UMOD. Copy number variation analysis of the NPHP1 gene using the commercially available MLPA kit identified a recurrent large homozygous deletion encompassing all NPHP1 exons. The parents were heterozygous for this deletion. Whole genome array-CGH analysis confirmed a homozygous deletion on chromosome 2q13, NPHP1 site, and revealed that the size of the copy number loss was approximately 102 Kbp.
  
  
  CONCLUSIONS
  This is the first report of determination of an NPHP1 deletion size using routine diagnostic methods. The results of this study expand the knowledge about the genotype-phenotype correlations in NPHP1, and have implications for genetic counseling and family planning advice for other affected families. This is the first molecular analysis of NPHP1 in an Iranian kindred.
authors.affiliation: The Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK. alireza.haghighi@genetics.med.harvard.edu.|Department of Genetics, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, 02115, USA. alireza.haghighi@genetics.med.harvard.edu.|Department of Medicine and the Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA, USA. alireza.haghighi@genetics.med.harvard.edu.
authors.forename: A
authors.initials: A
authors.lastname: Haghighi
authors.affiliation: Department of Medicine, Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Savaj
authors.affiliation: Faculty of Medicine, Mashhad Azad University, Mashhad, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Haghighi-Kakhki
authors.affiliation: Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Benoit
authors.affiliation: Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Grisart
authors.affiliation: Center for Human Genetics, Université Catholique de Louvain, Brussels, Belgium.|Institute of Pathology and Genetics, Gosselies, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Dahan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics*; D000328:Adult; D003598:Cytoskeletal Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000151:congenital* / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D017384:Sequence Deletion; D058949:Uromodulin / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C108725:NPHP1 protein, human; C548612:UMOD protein, human; D058949:Uromodulin
keywords: Deletion; Iran; NPHP; NPHP type 1; Nephronophthisis; Size determination