The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions–deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions–deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins.

Background Acute respiratory tract infections (ARTIs) are the most common indication for antibiotic prescriptions. This is associated with irrational prescription and correlated with antimicrobial resistance especially in low-income countries including Sudan. This is a cross-sectional study aimed at identifying bacterial pathogens causing ARTIs and their susceptibility to the commonly prescribed antibiotics. Methods Bacterial pathogens (51 isolates) were obtained from 29 ARTI patients from two hospitals in Khartoum in the time period March 2021 to March 2022. Samples were collected from each patient using both nasopharyngeal and oropharyngeal swabs. They were then cultured using blood and chocolate agar. The isolated colonies were identified using Gram staining technique, biochemical test, and selective media. Antibiotic susceptibility tests (AST) were done using the Kirby–Bauer disc diffusion susceptibility test protocol. Susceptible strains were determined following CLSI guidelines. The susceptibility of isolates was determined for different antibiotics representing the important classes including co-amoxiclav, cefixime, penicillin G, oxacillin, ceftriaxone, erythromycin, levofloxacin, ciprofloxacin and meropenem. Results Isolates were found to be mostly (82.3%) Gram positive (Staphylococcus aureus and Streptococcus pyogenes). Pseudomonas aeruginosa was the most abundant (17.9%) Gram-negative bacteria. S. aureus isolates were found to be 100% susceptible to levofloxacin, ciprofloxacin and meropenem. S. aureus exhibited less susceptibility to ceftriaxone (75%), and the least susceptibility to co-amoxiclav (37.5%), cefixime (31.3%), oxacillin (18.8) and erythromycin (25%). S. pyogenes isolates were found to be completely susceptible (100%) to co-amoxiclav, levofloxacin, ciprofloxacin and ceftriaxone. S. pyogenes had less susceptibility to vancomycin (92%), and the least susceptibility to cefixime (38.5%) and erythromycin (26.9%). P. aeruginosa isolates were found to be 100% susceptible to levofloxacin, ciprofloxacin and ceftriaxone, with less susceptibility to ceftriaxone (66%) and the least susceptibility to co-amoxiclav (22.2%), cefixime (33.3%), erythromycin (11.1%), vancomycin (11.1%) and oxacillin. Conclusions Co-amoxiclav is extensively used in Sudan empirically. The results show that S. aureus and P. aeruginosa are increasingly becoming resistant to this drug. However, S. pyogenes is still susceptible to it. Conversely resistance to erythromycin and cephalosporins is shown in all the different isolated species, however these drugs are still widely used without even culture and ASTs. Luckily, non-susceptibility to ciprofloxacin and levofloxacin was not detected here. Obviously, laboratory identification and ASTs are much needed along with surveillance programmes in hospitals. Together with rational use of antibiotics these measures will help to slow down the progress of the deadly AMR pandemic.

Background: Leber Congenital Amaurosis (LCA) is a clinically and genetically heterogeneous inherited retinal dystrophy characterized by early onset visual impairment caused by mutations in not less than 17 genes. AIPL1 mutations cause LCA type 4, comprising approximately 7% of LCA worldwide. The importance of establishing a genetic diagnosis lies in the promise of gene therapy demonstrated in mouse models. Results: we genetically investigated a consanguineous Sudanese family with Leber Congenital Amaurosis. Eight members of the family were affected. Using whole exome sequencing in two siblings and their healthy mother, both inheritance-based and phenotype-based prioritization strategies converged to identify a truncating variant (rs62637009) in AIPL1, consistent with a diagnosis of LCA type 4. AIPL1 c.487C>T is an ultra-rare cause of LCA4 that was seen previously in homozygous state in a single Palestinian family. This recurrent variant seems to have a regional importance with a likely founder effect. Conclusions: This report adds evidence to the pathogenicity of AIPL1 c.487C>T meriting its conclusive annotation as a recurrent pathogenic variant. This variant is particularly relevant to the middle-eastern and northeast African regions.