Outcomes and appropriateness of colonoscopy referrals at King Khalid University Hospital, Saudi Arabia: An opportunity to expand the colonoscopy screening.

OBJECTIVES: To examine the colonoscopy referrals in an open-access system and determine the outcome and factors associated with appropriate referral. METHODS: A retrospective study of colonoscopy referrals used patients' medical records at King Khalid University Hospital, Riyadh, Saudi Arabia, during 2020-2022. Fisher's exact or Pearson's Chi-squared test were used for data analysis. RESULTS: Out of 365 patients, 95.1% were referred from family medicine clinics with a mean age of 56.2±15.7 years. Men account for 53.2% of patients. The most common symptoms were change in bowel habits (35.6%), abdominal pain (30.4%), and anemia (20.1%). A family history of colorectal cancer was positive in 12.1%, while a personal history was positive in 4.4%. Most referrals (86.0%) were appropriate based on the American Society for Gastrointestinal Endoscopy (ASGE) guidelines. However, approximately 89.1% of patients aged ≥45 years had neoplasia and 40.0% had inflammatory bowel disease (p=0.019). The rank of the physicians (p=0.558) or the gender of the patients (p=0.665) did not influence the appropriateness. The inappropriate referrals were lower in patients with neoplasia (1.6%) than in patients with other lesions (p=0.002). CONCLUSION: The colonoscopy referrals were appropriate. The incidence of neoplasia was higher among those aged ≥45. Low inappropriate referrals and a high neoplasia detection were found based on ASGE guidelines. Future research should involve prospective multicenter referrals from family physicians outside hospitals and investigate patients' hesitancy to proceed with colonoscopy and cost-effectiveness.

Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan.

PINK1 is the second most predominant gene associated with autosomal recessive Parkinson's disease. Homozygous mutations in this gene are associated with an early onset of symptoms. Bradykinesia, tremors, and rigidity are common features, while dystonia, motor fluctuation, and non-motor symptoms occur in a lower percentage of cases and usually respond well to levodopa. We investigated 14 individuals with parkinsonism and eleven symptom-free siblings from three consanguineous Sudanese families, two of them multigenerational, using a custom gene panel screening 34 genes, 27 risk variants, and 8 candidate genes associated with parkinsonism. We found a known pathogenic nonsense PINK1 variant (NM_032409.3:c.1366C>T; p.(Gln456*)), a novel pathogenic single base duplication (NM_032409.3:c.1597dup; p.(Gln533Profs*29)), and another novel pathogenic insertion (NM_032409.3:c.1448_1449ins[1429_1443; TTGAG]; p.(Arg483Serfs*7)). All variants were homozygous and co-segregated in all affected family members. We also identified intrafamilial and interfamilial phenotypic heterogeneity associated with PINK1 mutations in these Sudanese cases, possibly reflecting the nature of the Sudanese population that has a large effective population size, which suggests a higher possibility of novel findings in monogenic and polygenic diseases in Sudan.

Methylation of alpha-synuclein in a Sudanese cohort.

BACKGROUND: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson's disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan. MATERIALS AND METHODS: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.6 ± 22.4 years). A family history of PD was evident in 64 patients. DNA preparation and bisulfite sequencing of SNCAintron1 was performed as described earlier. RESULTS: Of the fourteen analyzed CpGs of SNCAintron1, CpGs 16-23 were hypomethylated in PD (P-value ranged from 0.023 to 0.003). P-values improved, when sporadic cases were excluded from the analysis. CONCLUSION: We identified the presence of a specific pattern of DNA methylation in a young Sudanese cohort of familial PD, which confirms the importance of the methylation of SNCAintron1 for PD. This phenomenon appears to be independent of ethnicity, the impact of environmental factors, drug history, or familial clustering.