Publications by authors named "A Y Alzahrani"

453 Publications

A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population.

J Endocr Soc 2021 Aug 17;5(8):bvab095. Epub 2021 May 17.

Center for Genomic Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia.

Context: Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient.

Objective: This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman.

Methods: This study enrolled 22 patients from 13 unrelated families (2 families with 5 patients from Oman and 11 families with 17 patients from Saudi Arabia). All of these patients had presented within the first 10 days of life with nausea and vomiting, hyponatremia, hyperkalemia, and hypotension. We isolated DNA from peripheral blood and PCR-sequenced all exons and exon-intron boundaries of and, if negative, and using the Dideoxy Chain termination method.

Results: We found a total of 8 mutations in 13 families as follows: 6 mutations in , 1 in , and 1 in . All of these mutations were novel except one. mutations were: c.1496A>G, p.Q499R (novel) in 1 patient; c.1453C>T, p.Q485X (novel) in 1 patient; c.1322_1322delA, p.N441Tfs*41 (novel) in 2 patients of 1 family; c.876 + 2 delGAGT (novel) in 3 patients of 1 family; c.203_204 delTC, p.I68Tfs*76 (a known mutation) in 8 patients of 5 families; and whole gene deletion (novel) in 2 patients of 2 families. In addition, a nonsense mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family, and an deletion mutation c.527_528 delCA, p.T176Rfs*9 (novel) in 2 siblings from another Omani family.

Conclusion: We characterized a unique genotype of PHA 1b with several novel gene structure-disrupting mutations in , , and in a highly consanguineous population.
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http://dx.doi.org/10.1210/jendso/bvab095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272535PMC
August 2021

B-CATENIN ATTENUATION INHIBITS TUMOR GROWTH AND PROMOTES DIFFERENTIATION IN A BRAFV600E-DRIVEN THYROID CANCER ANIMAL MODEL.

Mol Cancer Ther 2021 Jun 17. Epub 2021 Jun 17.

Genetics, King Faisal Specialist Hospital and Research Centre

BRAFV600E mutation is the most frequent genetic alteration in papillary thyroid cancer (PTC). β-catenin (Ctnnb1) is a key downstream component of canonical Wnt signaling pathway and is frequently over-expressed in PTC. BRAFV600E-driven tumors have been speculated to rely on Wnt/β-catenin signaling to sustain its growth, although many details remain to be elucidated. In the present study, we investigated the role of β-catenin in BrafV600E-driven thyroid cancer in a transgenic mouse model. In BrafV600E mice with wild-type (wt) Ctnnb1 (BVE-Ctnnb1wt or BVE), over-expression of β-catenin was observed in thyroid tumors. In BrafV600E mice with Ctnnb1 knockout (BVE-Ctnnb1null), thyroid tumor growth was slowed with significant reduction in papillary architecture. This was associated with increased expression of genes involved in thyroid hormone synthesis, elevated 124Iodine uptake and serum T4. The survival of BVE-Ctnnb1null mice was increased by more than 50% during 14-month observation. Mechanistically, down-regulation of MAPK, PI3K/Akt, and TGF-β pathways and loss of epithelial-mesenchymal transition (EMT) were demonstrated in the BVE-Ctnnb1null tumors. Treatment with dual β-catenin/KDM4A inhibitor PKF118-310 dramatically improved the sensitivity of BVE-Ctnnb1wt tumor cells to BRAFV600E inhibitor PLX4720, resulting in significant growth arrest and apoptosis in vitro, and tumor regression and differentiation in vivo. These findings indicate that β-catenin signaling plays an important role in thyroid cancer growth and resistance to BRAFV600E inhibitors. Simultaneously targeting both Wnt/β-catenin and MAPK signaling pathways may achieve better therapeutic outcome in BRAFV600E inhibitor-resistant and/or radioiodine-refractory thyroid cancer.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0037DOI Listing
June 2021

Association between periodontitis and vitamin D status: A case-control study.

Saudi J Biol Sci 2021 Jul 20;28(7):4016-4021. Epub 2021 Apr 20.

Department of Basic Medical Science, Faculty of Applied Medical Sciences, Albaha University, 65779 Albaha, Saudi Arabia.

Vitamin D deficiency and periodontitis are commonly prevalent among Saudi adults. However, the association between periodontitis and vitamin D status has not been well documented. This study aims to examine the association between periodontitis and vitamin D status among adults in the Albaha region of Saudi Arabia. A case-control study of 123 Saudi adults was conducted; 60 had severe or moderate periodontitis, and 63 were periodontally healthy. Data was collected by an online self-reported sociodemographic questionnaire. All participants then underwent a full periodontal examination. Blood samples were also provided to assess participants' vitamin D statuses through serum levels of 25-hydroxyvitamin D (25(OH)D). A total of 60 cases and 63 controls matched for BMI (30.2 ± 4.86 kg/m), age (40.01 ± 7.73 years), and sex (46.3% and 53.7% male and female, respectively) participated in the study. Mean levels of 25(OH)D were significantly lower in periodontitis participants than in controls (25.03 ± 8.55 ng/ml, 29.19 ± 12.82 ng/ml,  = 0.037, respectively). Lower odds of periodontitis were detected per unit of 25(OH)D level (OR 0.964, 95% CI; 0.931-0.999,  = 0.043). In conclusion, periodontitis is significantly associated with deficient and insufficient levels of vitamin D among Saudi adults in the Albaha region. Future longitudinal research with a larger sample size may be suggested to confirm these results.
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http://dx.doi.org/10.1016/j.sjbs.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241627PMC
July 2021

Penetrating chest injury afflicting coronary artery fistula-A delayed and asymptomatic occurrence.

J Card Surg 2021 Jul 3. Epub 2021 Jul 3.

Cardiac Sciences Department, College of Medicine, King Fahad Cardiac Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.

We present here a case of a symptomatic chest injury with a nail gun causing a delayed occurrence of coronary artery fistula to the left pulmonary artery presenting with unstable angina 4 years after the initial injury, three of which were symptom-free. The patient underwent successful surgical closure of the fistula and removal of the foreign body.
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http://dx.doi.org/10.1111/jocs.15775DOI Listing
July 2021

Assessing knowledge and practice about eye injuries first aid, with awareness about the importance of early management among general population in Asser Region, 2020.

J Family Med Prim Care 2021 May 31;10(5):2022-2027. Epub 2021 May 31.

Department of Surgery, College of Medicine, King Khalid University, Abha, Saudi Arabia.

Background: Eye injury is a leading cause of monocular blindness and is second only to cataract as the commonest cause of visual impairment. Injury is the commonest reason for eye-related emergency department visits.

Aim: To assess population awareness regarding eye injuries first aids in Aseer region, Saudi Arabia.

Methodology: A descriptive cross-sectional approach was used targeting all accessible population in Aseer region, Southern of Saudi Arabia. Data were collected from participants using electronic pre-structured questionnaire. The tool will cover participants' socio-demographic data, participants' history of eye injury, awareness and practice regarding different types of eye injuries first aids.

Results: The survey included 1213 participants who completed the questionnaire. Participants' ages ranged from 18 to 60 years old with mean age of 22.3 ± 11.9 years old. About 69% of the participants reported for having constant eye pain, 68.3% reported in case of Foreign Body (FB) in the eye, 66.9% reported for torn eye lid. Regarding signs of scratch eye, 64.2% reported for feel FB inside, 58% reported for eye pain and 55.2% reported for blurred vision. Exact of 25.7% of participants reported that they should blink several times in case of getting eye scratch, whereas 77.8% reported that they should rub the eye to try to remove any foreign object, 36.3% preferred to use the soothing eye drop.

Conclusions: In conclusion, the study revealed that public awareness regarding eye injury first aid in Aseer region was poor especially for chemical injuries. Physician role should be augmented and health education campaigns are advised.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_2223_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208201PMC
May 2021