Mutational Screening Of The RB1 Gene In Pakistani Patients With Retinoblastoma (Record no. 6666)
[ view plain ]
| 000 -LEADER | |
|---|---|
| fixed length control field | 04479nam a22002297a 4500 |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20151207093137.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 151207b2015 xxu||||| |||| 00| 0 eng d |
| 041 ## - LANGUAGE CODE | |
| Language code of text/sound track or separate title | eng |
| 082 ## - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 2370-T |
| 100 ## - MAIN ENTRY--AUTHOR NAME | |
| Personal name | Saeeda Kalsoom (2007-VA-555) |
| 110 ## - MAIN ENTRY--CORPORATE NAME | |
| Location of meeting | Dr. Muhammad Wasim) |
| 245 ## - TITLE STATEMENT | |
| Title | Mutational Screening Of The RB1 Gene In Pakistani Patients With Retinoblastoma |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT) | |
| Year of publication | 2015 |
| 300 ## - PHYSICAL DESCRIPTION | |
| Number of Pages | 178p.; |
| 502 ## - DISSERTATION NOTE | |
| Dissertation 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. |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical Term | Department of Molecular Biology and Biotechnology |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical Term | Phd. Theses |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Dr. Khushnooda Ramzan |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Dr. Ali Raza Awan |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Dr. Aftab Ahmad Anjum |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Koha item type | Thesis |
| Damaged status | Collection code | Permanent Location | Current Location | Shelving location | Date acquired | Full call number | Accession Number | Koha item type |
|---|---|---|---|---|---|---|---|---|
| Veterinary Science | UVAS Library | UVAS Library | Thesis Section | 2015-12-07 | 2370-T | 2370-T | Thesis |