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This review discusses the discovery, epidemiology, pathophysiology, genetic etiology, molecular diagnosis, and medication-based management of fragile X syndrome (FXS). It also highlights the syndrome's variable expressivity and common comorbid and overlapping conditions. FXS is an X-linked dominant disorder associated with a wide spectrum of clinical features, including but not limited to intellectual disability, autism spectrum disorder, language deficits, macroorchidism, seizures, and anxiety. Its prevalence in the general population is approximately 1 in 5000–7000 men and 1 in 4000–6000 women worldwide. FXS is associated with the fragile X messenger ribonucleoprotein 1 (FMR1) gene located at locus Xq27.3 and encodes the fragile X messenger ribonucleoprotein (FMRP). Most individuals with FXS have an FMR1 allele with > 200 CGG repeats (full mutation) and hypermethylation of the CpG island proximal to the repeats, which silences the gene's promoter. Some individuals have mosaicism in the size of the CGG repeats or in hypermethylation of the CpG island, both produce some FMRP and give rise to milder cognitive and behavioral deficits than in non-mosaic individuals with FXS. As in several monogenic disorders, modifier genes influence the penetrance of FMR1 mutations and FXS's variable expressivity by regulating the pathophysiological mechanisms related to the syndrome's behavioral features. Although there is no cure for FXS, prenatal molecular diagnostic testing is recommended to facilitate early diagnosis. Pharmacologic agents can reduce some behavioral features of FXS, and researchers are investigating whether gene editing can be used to demethylate the FMR1 promoter region to improve patient outcomes. Moreover, clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 and developed nuclease defective Cas9 (dCas9) strategies have promised options of genome editing in gain-of-function mutations to rewrite new genetic information into a specified DNA site, are also being studied. [ABSTRACT FROM AUTHOR]

Background. Coronary artery diseases may be affected by several genetic and nongenetic factors. Single‐nucleotide polymorphism (SNP) rs599839 and type 2 diabetes mellitus (T2DM) can affect the occurrence and severity of coronary artery disease (CAD). Methods. Our aim was to investigate how T2DM and the rs599839 variant affected serum lipid levels and the degree of CAD patients' coronary artery stenosis. rs599839 polymorphism genotyping was done on Saudi patients with coronary angiography performed previously. Patients enrolled were divided into group A (360 DM patients), group B (225 DM patients with CAD), and group C (190 healthy volunteers as control). Results. Individuals with diabetes and CAD who possessed the GG genotype in rs599839 exhibited markedly reduced means of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), and triglycerides (TG; 224.5, 116.2, and 221.4 versus 251.6, 131.3, and 261.7 mg/dl, p = 0.003, 0.007, and 0.025, respectively) than AA genotype. The odds ratio and the confidence interval of 95% for G allele carriers of rs599839 were OR = 0.62, 95% CI: 0.41–0.82, and p = 0.003, among diabetic patients with CAD. Conclusions. In patients with diabetic CAD, the locus 1p13.3 polymorphism rs599839 was found to be substantially correlated with serum lipid levels. Furthermore, among Saudi patients with diabetes, the G allele of rs599839 variant lowers the CAD risk. [ABSTRACT FROM AUTHOR]

Background: The  PSMB8  and  PSMB9  immunoproteasome   genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in  PSMB9  and  PSMB8 . We determined any associations between these SNPs and susceptibility to UBC in the Saudi community., Methods: Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the  PSMB9  rs17587 G>A and  PSMB8  rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model., Results: The  PSMB9  rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21,  P  < 0.0001). In contrast, the  PSMB8  rs2071543 SNP showed no association with UBC risk (OR = 1.13,  P  = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1;  P  = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4;  P  = 0.0026) models. Genotypic distribution of the  PSMB8  rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models ( P  > 0.05)., Conclusion: These results suggest a potential role for  PSMB9  as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Elhawary et al.)

Translocation of sex/autosome chromosomes is uncommon, but they have a stronger impact on fertility than autosome/autosome translocation.   Y/autosome translocation is associated with azoospermia in 80% of cases. To our knowledge, there have been only eight cases reported of a balanced reciprocal (Y;16) translocation associated with male infertility.Here we report an infertile man with azoospermia who has a reciprocal translocation t(Y;16) (q12; p13.2).  A 38-year-old Saudi medically free male presented with primary infertility and azoospermia for six years. He has a positive family history of male infertility. Physical examination was unremarkable. Investigations showed normal hormonal panel and azoospermia. He has a male karyotype with a reciprocal chromosome Y,16 translocation. Histopathology report of bilateral testicular sperm extraction (TESE) revealed most tubules show early maturation arrest and few show either Sertoli-cell only syndrome or are completely hyalinized and atrophic.  This case illustrates a rare cause of non-obstructive azoospermia in a male with chromosome Y,16 translocation as a result of a meiotic arrest. Medical practitioners should be aware of the genetic abnormalities of male patients who present with primary infertility. Karyotyping has the capability to diagnose genetic abnormalities in this patient., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alharbi et al.)