PMID- 26396485
OWN - NLM
STAT- MEDLINE
DCOM- 20160624
LR  - 20221207
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 21
DP  - 2015
TI  - Alterations in the RB1 gene in Pakistani patients with retinoblastoma using 
      direct sequencing analysis.
PG  - 1085-92
AB  - PURPOSE: Retinoblastoma (RB) is a rare intraocular malignant tumor of the 
      developing retina with an estimated incidence of 1:20,000 live births in children 
      under the age of 5 years. In addition to the abnormal whitish appearance of the 
      pupil or leukocoria, strabismus has also been reported as a clinical symptom of 
      the disease. RB1 is the first cloned tumor suppressor gene, and mutational 
      inactivation of this gene is responsible for the development of RB during early 
      childhood. The purpose of this study was to identify mutational alterations in 
      the RB1 gene in Pakistani patients with RB. METHODS: During this study, 70 
      clinically evaluated patients with RB were recruited from different regions of 
      Pakistan. The cases included 23 sporadic bilateral (32.9%), 34 sporadic 
      unilateral (48.6%), nine familial bilateral (12.8%), and four familial unilateral 
      (5.7%) cases. Constitutional causative mutations in the RB1 gene were screened 
      via direct sequencing of all RB1 exons and their flanking regions. RESULTS: In 
      this report, genetic testing resulted in the identification of 18 mutations in 25 
      patients with RB including six novel RB1 mutations. Of the total mutations 
      identified, 13 (72.22%) were found to be null mutations caused by nine nonsense, 
      three deletions, and one insertion. Two (11.11%) missense, two (11.11%) splice 
      site mutations, and one (5.55%) base substitution in the promoter region were 
      also found. Moreover, ten intronic variants were identified, one of which is 
      novel. CONCLUSIONS: Molecular screening and identification of these mutations in 
      Pakistani patients with RB provide the mutational variants of the RB1 gene in the 
      Pakistani population. The detection of oncogenic mutations in patients with RB 
      and genetically predisposed individuals is a major step in clinical management, 
      prognosis, follow-up care, accurate genetic counseling, and presymptomatic 
      diagnosis of RB.
FAU - Kalsoom, Saeeda
AU  - Kalsoom S
AD  - Institute of Biochemistry and Biotechnology, University of Veterinary and Animal 
      Sciences, Lahore, Pakistan ; Institute of Molecular Biology and Biotechnology, 
      The University of Lahore, Pakistan.
FAU - Wasim, Muhammad
AU  - Wasim M
AD  - Institute of Biochemistry and Biotechnology, University of Veterinary and Animal 
      Sciences, Lahore, Pakistan.
FAU - Afzal, Sibtain
AU  - Afzal S
AD  - Prince Naif Center for Immunology Research, College of Medicine, King Saud 
      University, Riyadh, Saudi Arabia ; BioTech Labs, Chemhouse, Lahore, Pakistan.
FAU - Shahzad, Muhammad Saqib
AU  - Shahzad MS
AD  - Center for Research in Molecular Medicine, The University of Lahore, Pakistan.
FAU - Ramzan, Shaiqa
AU  - Ramzan S
AD  - BioTech Labs, Chemhouse, Lahore, Pakistan.
FAU - Awan, Ali Raza
AU  - Awan AR
AD  - Institute of Biochemistry and Biotechnology, University of Veterinary and Animal 
      Sciences, Lahore, Pakistan.
FAU - Anjum, Aftab Ahmed
AU  - Anjum AA
AD  - Department of Microbiology, University of Veterinary and Animal Sciences, Lahore, 
      Pakistan.
FAU - Ramzan, Khushnooda
AU  - Ramzan K
AD  - BioTech Labs, Chemhouse, Lahore, Pakistan ; Department of Genetics, King Faisal 
      Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150917
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Asian People
MH  - Base Sequence
MH  - Child
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Exons
MH  - Female
MH  - Gene Expression
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Infant
MH  - Introns
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pakistan
MH  - Pedigree
MH  - Prognosis
MH  - Retina/metabolism/pathology/surgery
MH  - Retinal Neoplasms/ethnology/*genetics/pathology/surgery
MH  - Retinoblastoma/ethnology/*genetics/pathology/surgery
MH  - Retinoblastoma Protein/*genetics
PMC - PMC4575903
EDAT- 2015/09/24 06:00
MHDA- 2016/06/25 06:00
PMCR- 2015/01/01
CRDT- 2015/09/24 06:00
PHST- 2014/12/31 00:00 [received]
PHST- 2015/09/15 00:00 [accepted]
PHST- 2015/09/24 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/06/25 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 97 [pii]
PST - epublish
SO  - Mol Vis. 2015 Sep 17;21:1085-92. eCollection 2015.