title: Genetic screening in Iranian patients with retinoblastoma.
abstract: PurposeThe most common intraocular tumor in childhood, retinoblastoma, is largely associated with mutations in the RB1 gene. In the most comprehensive RB1 screening in Iran, we evaluated the RB1 mutations in 106 patients with retinoblastoma, including 73 bilateral (heritable) and 33 unilateral (sporadic) cases.Patients and methodsMutations were identified using amplification refractory mutation system (ARMS) PCR and direct sequencing of the 27 coding exons of RB1 and multiplex ligation-dependent probe amplification (MLPA).Results and ConclusionWe found 33 (31%) and 64 (60%) patients with sporadic unilateral and bilateral retinoblastoma, respectively as well as 9 (8.5%) cases with hereditary bilateral retinoblastoma. In total, we identified 52 causative RB1 mutations in 106 patients (global mutation rate of 49%). Of the 52 patients, 48 (92%) had sporadic and familial bilateral and 4 (8%) had sporadic unilateral RB. Therefore, the detection rate of RB1 mutations was 66% (48/73) and 12% (4/33) in bilateral and unilateral cases, respectively. Mutations were classified as nonsense in 31 (60%), missense in 1 (2%), large deletion in 11 (21%), small deletion in the 7 novel (15%) and splice site mutation in 2 (4%) patients with RB. Of 31 nonsense mutations, 23 (74%) occurred in the 11 Arginine codons of the RB1. Seven mutations (13%) were novel, and 45 (87%) had been previously reported. Thirty-three mutations were single-base substitutions leading to 31 nonsense amino acid changes and 2 splice site mutations in introns 12 and 16 of RB1. The altered 3D model structures of the RB1 novel mutant proteins are also predicted in this study.
authors.affiliation: Department of Ophthalmology and Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: K
authors.initials: K
authors.lastname: Shahraki
authors.affiliation: Reproductive Biotechnology Research Center, Avicenna Research Institute, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Ahani
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, Rassoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Faranoush
authors.affiliation: Department of Pediatrics, Ali Asghar Children Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: G
authors.initials: G
authors.lastname: Bahoush
authors.affiliation: Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: I
authors.initials: I
authors.lastname: Torktaz
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, MD, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: Department of Ophthalmology and Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Naseripour
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, MD, USA.|Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS) Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Behnam
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007492:Iran / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D012160:Retina / Q000473:pathology; D019572:Retinal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012175:Retinoblastoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D018389:Codon, Nonsense