title: CTNS molecular genetics profile in a Persian nephropathic cystinosis population.
abstract: OBJECTIVE
  In this report, we document the CTNS gene mutations of 28 Iranian patients with nephropathic cystinosis age 1-17 years. All presented initially with severe failure to thrive, polyuria, and polydipsia.
  
  
  METHODS
  Cystinosis was primarily diagnosed by a pediatric nephrologist and then referred to the Iran University of Medical Sciences genetics clinic for consultation and molecular analysis, which involved polymerase chain reaction (PCR) amplification to determine the presence or absence of the 57-kb founder deletion in CTNS, followed by direct sequencing of the coding exons of CTNS.
  
  
  RESULTS
  The common 57-kb deletion was not observed in any of the 28 Iranian patients. In 14 of 28 patients (50%), mutations were observed in exons 6 and 7. No mutation was detected in exon 5, and only one (3.6%) patient with cystinosis showed a previously reported 4-bp deletion in exon 3 of CTNS. Four patients (14.3%) had a previously reported mutation (c.969C>A; p.N323K) in exon 11, and five (18%) had novel homozygous deletions in exon 6 leading to premature truncation of the protein. These deletions included c.323delA; p.Q108RfsX10 in three individuals and c.257-258delCT; p.S86FfsX37 in two cases. Other frame-shift mutations were all novel homozygous single base pair deletion/insertions including one in CTNS exon 9 (c.661insT; p.V221CfsX6), and four (14.3%) in exon 4, i.e., c.92insG; p.V31GfsX28 in two and c.120delC; p.T40TfsX10 in two. In total, we identified eight previously reported mutations and eight novel mutations in our patients. The only detected splice site mutation (IVS3-2A>C) was associated with the insertion mutation in the exon 9.
  
  
  CONCLUSIONS
  This study, the first molecular genetic analysis of non-ethnic-specific Iranian nephropathic cystinosis patients, may provide guidance for molecular diagnostics of cystinosis in Iran.
authors.affiliation: Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Farideh
authors.initials: F
authors.lastname: Ghazi
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ali Asghar Children Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Rozita
authors.initials: R
authors.lastname: Hosseini
authors.affiliation: Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Akouchekian
authors.affiliation: Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Teimourian
authors.affiliation: Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Ataei Kachoei
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ali Asghar Children Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Otukesh
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Pediatrics, Faculty of Medicine, Ali Asghar Children Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran; Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, USA. Electronic address: Babak.Behnam@nih.gov.
authors.forename: Babak
authors.initials: B
authors.lastname: Behnam
mesh_terms: D000293:Adolescent; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003554:Cystinosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007492:Iran; D008297:Male; D009154:Mutation
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human
keywords: CTNS; Cystinosis; Iran; Irán; Mutación; Mutation; Novel; Nuevo; cistinosis