1.
Mutational Screening Of The RB1 Gene In Pakistani Patients With Retinoblastoma
by Saeeda Kalsoom (2007-VA-555) | Dr. Muhammad Wasim) | Dr. Khushnooda Ramzan | Dr. Ali Raza Awan | Dr. Aftab Ahmad Anjum.
Material type: ; Literary form:
not fiction
Publisher: 2015Dissertation note: Retinoblastoma is a neonatal intraocular tumor caused by biallelic inactivation of RB1 gene. Rb
patients and asymptomatic carriers undergo a series of clinical tests for diagnosis and tumor
treatment. These clinical examinations prove to be expensive and time consuming. On the other
hand if the proband’s RB1 gene mutation status is determined by genetic testing, it can prove as
more significant and cost effective diagnostic methods. Secondly, only those asymptomatic or at
risk carriers with the mutation, require clinical surveillance while those proven to be unaffected
do not require additional clinical examinations. Furthermore early diagnosis of Rb by molecular
testing can enable and enhance clinical management, earlier treatment, follow-up care, carrier
screening, genetic counseling, prenatal diagnosis and reproductive planning in predisposed
families. Irrespective of the importance of molecular testing of Rb patients, in Pakistan only a
few clinical reports on Rb are available so, there was a dire need to find RB1 mutations in
Pakistani Rb patients and to set a molecular based diagnosis for poor affected families. Keeping
in view the importance of molecular diagnosis, in this study a reliable genetic test has been
developed to detect the RB1 germline mutations in Pakistani Rb patients.
During this study, 70 Rb patients including 38 unilateral and 32 bilateral cases were enrolled,
from different regions of Pakistan. By using direct sequencing method, seven novel and twelve
reported RBI mutations were found. The novel mutations included three frameshift mutations
(c.1116_1119delCACT in exon 11, c.1436_1437delAC in exon 16 and c.2060_2061insTCATT
in exon 20) and four substitutions (c.148G>T in exon 2, c.610G>T in exon 2, g.94G>C in exon
7, c.947A>T in exon 10 and g.1991G>C in promoter region) while twelve reported mutations in
146
22 patients included, 9 substitutions (c.160G>T in exon 2, c.289G>T in exon 3, c.751C>T in
exon 8, c.920C>T in exon 9, c.967G>T in exon 10, c.1072C>T in exon 11, c.1654C>T in exon
17, c.2063T>C in exon 20 and c.2359C>T in exon 23), one frameshift mutation (c.772_776del in
exon 8) and two splice site mutations (c.380+1G>T and c.1215+1G>A in intron 3 and 12
respectively). Mutation detection rate was found to be 77.8% in (7/9) bilateral familial, 50% in
(2/4) unilateral familial, 56.5% in (13/23) bilateral sporadic and 14.7% in (5/34) unilateral
sporadic patients while overall rate of mutations in bilateral and unilateral patients was detected
as 62.5% (20/32) and 18.4% (7/38) respectively. Beside mutations one novel c.940-64C>T
(intron 9) and nine reported intronic variants c.380+45 C>T (intron 3), c.501-77G>A (intron 4),
c.1128-72T>G (intron 11), c.1695+99A>T (intron 17), c.1695-1696delAA (intron 17), c.1815-
104A>G (intron 18), c.1961-10T>C (intron 19), c.2663+33T>C (intron 25) and c.2664-10T>A
(intron 25) were also found. Carrier screening facility was also provided to six asymptomatic
siblings (as possible carriers) of familial proband but none of them was found to be diseased.
Hopefully, in future the findings and developed protocol of this study will help to reveal the
molecular basis of Rb in Pakistani Rb patients which additionally help to secure vision and life
of Rb patients. Further, in Pakistan there is dire need to develop “National Rb Registry Centre”,
to register all new Rb cases for finding incidence rate and prevalence of Rb in Pakistan. Beside
this other related issues like financial constraints, health education, planning and awareness
about Rb, occupational training for health providers, capacity building for neonatal
ophthalmologic screening and cosmetic rehabilitation for surviving Rb patients are important and
should consider. Availability: Items available for loan: UVAS Library [Call number: 2370-T] (1).
2.
Identification And Expression Analysis Of Genes Involved In Obsessive Compulsive Disorder In Pakistani Population
by Javeria (2008-VA-627) | Prof. Dr. Masroor Ellahi Babar | Dr. Muhammad Wasim | Prof. Dr. Muhammad Abdullah.
Material type: ; Literary form:
not fiction
Publisher: 2016Dissertation note: The background of this study is that WHO reports that psychiatry disorders affect worldwide 0.8 to 2% population. Anxiety illnesses are a class of illness associated with unreasonable and disturbing sensation of fear and tension. There are several types of anxiety disorders, such as panic disorder, agoraphobia, specific phobia, social phobia, OCD. Obsessive-compulsive disorder is a chronic disabling condition. OCD is characterized by repetitive, intrusive thoughts, images, and impulses and by repetitive, ritualistic physical or mental acts performed to reduce the attendant anxiety. The severity of OCD depends on the amount obsessions and compulsions. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a reliable and consistent scoring system that can be used to categorize OCD. The major genes involve in OCD are SLC6A4, BDNF, SLC1A1 and COMT genes.
The study was enrolled patients treated for OCD. Blood samples have been collected from the patients. DNA extracted from fresh blood. Primers were designed. Then DNA amplification have done by Bio-Rad thermal cycler. Then gel electrophoresis was done for PCR product quantification. PCR products precipitated and sequenced. SNPs were identified. Real-time quantitative RT-PCR was performed for each sample with TaqMan Universal PCR mastermix which showed down regulation of COMT gene in OCD patients in Pakistani population.
The aim of this study was SNP identification in Pakistani Population in Obsessive Compulsive disorder and to analyze the gene expression of COMT gene involved in OCD in Pakistani Population.
Availability: Items available for loan: UVAS Library [Call number: 2620-T] (1).
