Publications by authors named "Salma Majid Wakil"

6 Publications

  • Page 1 of 1

Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population.

Genomics 2020 03 31;112(2):1746-1753. Epub 2019 Oct 31.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. Electronic address:

Sanger Sequencing and immunohistochemistry was employed to investigate the TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in over 2200 samples of Middle Eastern origin from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancer (68.6%), followed by central nervous system tumors (28.7%), thyroid cancer (15.4%), prostate cancer (9.3%), endometrial carcinoma (3.7%), rhabdomyosarcoma (1.4%), colorectal cancer (1%), epithelial ovarian carcinoma (0.7%) and breast cancer (0.7%). No mutations were observed in other types of cancers. In bladder cancer, we found significant inverse association with metastasis and a trend to good survival in patients with TERT mutations. In gliomas, TERT promoter mutations predicted poor prognosis. In thyroid cancer, high frequency of TERT mutation was observed in poorly differentiated carcinoma. In addition, TERT promoter mutations were associated with aggressive markers and poor outcome in follicular thyroid carcinomas.
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http://dx.doi.org/10.1016/j.ygeno.2019.09.017DOI Listing
March 2020

Design of Arab Diabetes Gene-Centric Array (ADGCA) in population with an epidemic of Type 2 Diabetes: A population specific SNP evaluation.

Gene 2018 Jul 22;663:157-164. Epub 2018 Apr 22.

University Diabetes Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

In the case of diabetes and other complex diseases, the challenge has always been to find genetic markers that explain the excess risk associated with development of the disease. In the last 12 years, advances in genotyping technology provided substantial development in the discovery of loci contributing to Type 2 diabetes (T2D) susceptibility. Therefore, the aim of this study is to custom design, for the first time in Arab world, an "Arab Diabetes Gene Centric Array" (ADGCA) that assays 643, 745 SNP markers including 50,617 diabetes associated SNPs. The array content was designed after comprehensive literature search prioritizing Diabetes associated SNPs. PCA was performed to evaluate the relationship between world populations and the Saudi population in building the backbone for the array. A genotype data matrix for PCA analysis was produced by including the genotypes of the 270 HapMap samples including JPT, CHB, YRI and CEU to genotypes of the 1457 Saudi samples. Imputation was executed using IMPUTE2 software and the 1000GP Phase III reference panel. All markers incorporated to ADGCA were validated. Quality checks and evaluation of its capacity and performance as a platform for genetic screening for T2D was performed using the latest stastical tools available. We were successful in designing ADGCA as a custom made chip array designed with a motive to capture genetic variation in loci known or reported to be associated with the development of T2D. However, implementation of ADGCA is currently being performed by our research group using 2000 DNA samples respectively from diabetic and non diabetic individuals which could further validate the use of ADGSA in genetic screening of T2D.
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http://dx.doi.org/10.1016/j.gene.2018.04.019DOI Listing
July 2018

Pregnancy reduces severity and frequency of attacks in hyperkalemic periodic paralysis due to the mutation c.2111C>T in the gene.

Ann Indian Acad Neurol 2017 Jan-Mar;20(1):75-76

Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria.

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http://dx.doi.org/10.4103/0972-2327.194312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341276PMC
March 2017

Stroke-like episodes, peri-episodic seizures, and MELAS mutations.

Eur J Paediatr Neurol 2016 Nov 13;20(6):824-829. Epub 2016 Aug 13.

Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Purpose: Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC hyperintensity) or partial cytotoxic oedema (DWI hyperintensity, ADC hypointensity) in the acute and subacute stage, and with gyriform T1-hyperintensity (cortical necrosis) in the chronic stage.

Principal Results: SLEs must be clearly distinguished from ischaemic stroke, since management of these two entities is different. SLEs may go along with or without seizures or epileptiform discharges on EEG. However, in MELAS syndrome seizures may also occur in the absence of SLEs. Focal and generalised seizures have been reported but it is currently unknown if the one or the other prevail. SLEs with and without seizures may respond to NO-precursors l-arginine, succinate, or citrulline. As a supportive measure a ketogenic diet should be initiated. Seizures prior to or during a SLE or paroxysmal EEG-activity during a SLE should be initially treated with antiepileptic drugs (AEDs) with low mitochondrion-toxicity. Only in case these AEDs are ineffective, AEDs with higher mitochondrion-toxicity should be added.

Major Conclusions: All patients with SLEs need to have an EEG recorded irrespective if they have manifesting seizures or not. There are no mtDNA or nDNA mutations which predispose for SLEs with seizures.
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http://dx.doi.org/10.1016/j.ejpn.2016.08.002DOI Listing
November 2016

New analytical application of antibody-based biosensor in estimation of thyroid-stimulating hormone in serum.

Bioanalysis 2016 Apr 15;8(7):625-32. Epub 2016 Mar 15.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.

Background: Conventionally, ELISA is used to measure thyroid-stimulating hormone (TSH) for diagnosis of thyroid disease. In this study, an immunosensor-based, kinetic-exclusion analysis (KinExA) was used for TSH estimation.

Methodology: A PMMA microbead column coated with TSH antigen is formed inside the flow cell. Samples consisting of mouse anti-TSH monoclonal antibody and TSH antigen complex in solution are passed over the beads and the unbound anti-TSH antibody is captured by the TSH-coated beads, followed by passing fluorescent-labeled antibody over the beads to generate signals for analysis. The limit of detection for the assay was 0.4 mIU l(-1) and the precision was acceptable.

Conclusion: The developed sensor was advantageous due to the automated nature and its convenience, without compromising the sensitivity for estimation of TSH.
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http://dx.doi.org/10.4155/bio-2015-0034DOI Listing
April 2016

Unbiased targeted next-generation sequencing molecular approach for primary immunodeficiency diseases.

J Allergy Clin Immunol 2016 06 23;137(6):1780-1787. Epub 2016 Feb 23.

Department of Genetics (Research Center), King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.

Background: Molecular genetics techniques are an essential diagnostic tool for primary immunodeficiency diseases (PIDs). The use of next-generation sequencing (NGS) provides a comprehensive way of concurrently screening a large number of PID genes. However, its validity and cost-effectiveness require verification.

Objectives: We sought to identify and overcome complications associated with the use of NGS in a comprehensive gene panel incorporating 162 PID genes. We aimed to ascertain the specificity, sensitivity, and clinical sensitivity of the gene panel and its utility as a diagnostic tool for PIDs.

Methods: A total of 162 PID genes were screened in 261 patients by using the Ion Torrent Proton NGS sequencing platform. Of the 261 patients, 122 had at least 1 known causal mutation at the onset of the study and were used to assess the specificity and sensitivity of the assay. The remaining samples were from unsolved cases that were biased toward more phenotypically and genotypically complicated cases.

Results: The assay was able to detect the mutation in 117 (96%) of 122 positive control subjects with known causal mutations. For the unsolved cases, our assay resulted in a molecular genetic diagnosis for 35 of 139 patients. Interestingly, most of these cases represented atypical clinical presentations of known PIDs.

Conclusions: The targeted NGS PID gene panel is a sensitive and cost-effective diagnostic tool that can be used as a first-line molecular assay in patients with PIDs. The assay is an alternative choice to the complex and costly candidate gene approach, particularly for patients with atypical presentation of known PID genes.
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http://dx.doi.org/10.1016/j.jaci.2015.12.1310DOI Listing
June 2016