Molecular Screening of <i>VAX1</i> Gene Polymorphisms Uncovered the Genetic Heterogeneity of Non-Syndromic Orofacial Cleft in Saudi Arabian Patients

Objective: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP. Methods: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect. Results: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: odds ratio [OR] 2.16 [95% CI 1.38–3.4]; mothers: OR 2.39 [95% CI 1.53–3.71]; and infants: OR 2.77 [95% CI 1.77–4.34]) and CP (fathers: OR 2.24 [95% CI 1.15–4.36] and infants: OR 2.43 [95% CI 1.25–4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05–2.86]; mothers: OR 2.43 [95% CI 1.49–3.97]; and infants: OR 2.34 [95% CI 1.44–3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls (p = 0.001). Conclusion: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity

Association of Polymorphism of the Methyl Tetrahydrofolate Reductase (MTHFR) Gene with Anti-Seizure Medication Response in Pediatric Patients in Jeddah, Saudi Arabia

Background and Objectives: Epilepsy is a chronic brain disease, with inherent and noninherent factors. Although over 20 anti-seizure medications (ASMs) are commercially available, nearly one-third of patients develop drug-resistant epilepsy. We evaluated the association between the clinical features and the methyl tetrahydrofolate (MTHFR) rs1801133 polymorphism and ASMs response among pediatric patients with epilepsy. Materials and Methods: This was a multicenter, retrospective, case&ndash;control study of 101 children with epilepsy and 59 healthy children in Jeddah. The MTHFR rs1801133 polymorphism was genotyped using the real-time polymerase chain reaction TaqMan Genotyping Assay. Results: Among the patients with epilepsy, 56 and 45 showed good and poor responses to ASMs, respectively. No significant genetic association was noted between the single-nucleotide polymorphism (SNP) rs1801133 within the MTHFR gene and the response to ASMs. However, a significant association was noted between reports of drug-induced toxicity and an increase in allele A frequencies. The MTHFR rs1801133 genotype was significantly associated with the development of electrolyte disturbance among good and poor responders to ASMs. Conclusions: This is the first pharmacogenetic study of MTHFR in patients with epilepsy in Saudi Arabia that found no significant association between the MTHFR SNP rs1801133 and gene susceptibility and drug responsiveness. A larger sample size is needed for testing gene polymorphisms in the future

Next generation sequencing shows diversity of Omicron sub-lineages of SARS-COV2 circulating in Jeddah, Saudi Arabia

The ever-evolving Omicron variant of the SARS-CoV-2 and its sub-lineages have prompted Saudi Arabia to continuously track circulating lineages. We focused on the presence of diverse SARS-CoV-2 circulation in Saudi Arabia and presented the whole genome sequencing study of 94 positive SARS-CoV-2 specimens procured between February and April 2022 in the city of Jeddah, Saudi Arabia. Following whole-genome sequencing, bioinformatics analysis was undertaken. The SARS-CoV-2 variant Omicron clades 21K and 21L constituted the entirety of sequenced specimens, belonging to BA.2 (n = 56) and BA.1.1 (n = 20), respectively, and low-frequency sub-lineages were BA.2.3 (n = 6), BA.1 (n = 4), BA.2.40.1 (n = 2), BA.1.14 (n = 1), BA.2.10 (n = 1), BA2.32 (n = 1), BA.2.57 (n = 1), BA2.64 (n = 1), and BA2.5 (n = 1). Mutational patterns were identified, as well as possible consequences for the spread of the virus. Comparative molecular docking of Omicron-specific Nucleocapsid protein harboring the mutations P13L, R203K, G204R, as well as S413R, and the deletions E31-, R32-, and S33- showed reduced interaction with human RIG-I protein with 8 interacting amino acid residues and 10 polar interactions, while the SARS-CoV-2 Nucleocapsid protein exhibited 15 interacting amino acid residues and 26 polar interactions. Ongoing monitoring is essential for assessing the genomic epidemiological consequences of tourist travel and pilgrimage in Jeddah and across Saudi Arabia, as well as the prompt identification of emerging variants for further investigation