A homozygous loss-of-function C1S mutation is associated with Kikuchi-Fujimoto disease.

BACKGROUND: Kikuchi-Fujimoto disease (KFD) is a self-limited inflammatory disease of unknown pathogenesis. Familial cases have been described and defects in classical complement components C1q and C4 have been identified in some patients. MATERIAL AND METHODS: We describe genetic and immune investigations of a 16 years old Omani male, a product of consanguineous marriage, who presented with typical clinical and histological features of KFD. RESULTS: We identified a novel homozygous single base deletion in C1S (c.330del; p. Phe110LeufsTer23) resulting in a defect in the classical complement pathway. The patient was negative for all serological markers of SLE. In contrast, two female siblings (also homozygous for the C1S mutation), one has autoimmune thyroid disease (Hashimoto thyroiditis) and a positive ANA and the other sibling has serology consistent with SLE. CONCLUSION: We report the first association between C1s deficiency and KFD.

Molecular blood group screening in Omani blood donors.

BACKGROUND AND OBJECTIVES: Blood group genotyping has been used in different populations. This study aims at evaluating the genotypes of common blood group antigens in the Omani blood donors and to assess the concordance rate with obtained phenotypes. MATERIAL AND METHODS: Blood samples from 180 Omani donors were evaluated. Samples were typed by serological methods for the five blood group systems MNS, RH (RHD/RHCE), KEL, FY and JK. Samples were genotyped using RBC-FluoGene vERYfy eXtend kit (inno-train©). Predicted phenotypic variants for 70 red blood cell antigens among the MNS, RH (RHD/RHCE), KEL, FY, JK, DO, LU, YT, DI, VEL, CO and KN blood group systems were assessed. RESULTS: Simultaneous phenotype and genotype results were available in 130 subjects. Concordance rate was >95% in all blood group systems with exception of Fy(b+) (87%). Homozygous GATA-1 mutation leading to erythroid silencing FY*02N.01 (resulting in the Fy(b-)ES phenotype) was detected in 81/112 (72%) of genotyped samples. In addition, discrepant Fyb phenotype/genotype result was obtained in 14/112 samples; 13 of which has a heterozygous GATA-1 mutation and one sample with a wild GATA genotype. D and partial e c.733C>G variants expressing the V+VS+ phenotype were found in 22/121 (18.2%) and 14/120 (11.7%) of the samples, respectively. Di(a-b+), Js(a-b+), Yt(a+b-) and Kn(a+b-) genotype frequencies were 99.4%, 95.8%, 91.9% and 97.7%, respectively. CONCLUSION: In conclusion, we report a high frequency of FY*02N.01 allele due to homozygous c.-67T>C GATA-1 single-nucleotide variation. This is the first study reporting the detailed distribution of common and rare red cell genotypes in Omani blood donors.

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation.

BACKGROUND: Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT. METHODS: This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes. RESULTS: A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively). CONCLUSIONS: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

Inferior lead discordance in ventricular arrhythmias: A specific marker for certain arrhythmia locations.

BACKGROUND: Most idiopathic ventricular arrhythmias (VAs) originate from the outflow tracts and are characterized by an inferior axis on the 12-lead ECG. A group of patients will exhibit inferior lead discordance (ILD), demonstrating a positive QRS in lead II with negative QRS in III or the opposite finding. METHODS AND RESULTS: We identified patients undergoing ablation of idiopathic premature ventricular contractions (PVCs) or ventricular tachycardia (VT) between 2013 and 2015. The site of earliest activation was determined using electroanatomic mapping and intracardiac echocardiography. Out of 281 patients, 25 (8.9%) exhibited ILD. In patients with positive/negative discordance (n = 18), the source was mapped to the parahisian region in 14 cases and to the right ventricular (RV) moderator band (MB) or papillary muscles (PMs) in 4, while all those with negative/positive discordance (n = 7) were mapped to the anterolateral PM (ALPM). In the group with positive/negative discordance, a later precordial transition (>V4), wider QRS duration, and the presence of notch in the inferior leads pointed toward a RV MB/PM origin. Complete PVC/VT suppression was achieved in 72%. In 2 patients with parahisian PVCs, ablation was not attempted due to risk of heart block. CONCLUSIONS: The presence of ILD is associated with particular anatomical locations, namely, the parahisian region, RV MB/PM, and ALPM. The outcomes of ablation are more modest compared to other idiopathic VAs, reflecting the technical difficulties associated with these anatomical locations, such as the proximity to the conduction system in parahisian VAs or stability issues when ablating the PMs or MB.

Characterization of Blood Group Variants in an Omani Population by Comparison of Whole Genome Sequencing and Serology.

Although blood group variation was first described over a century ago, our understanding of the genetic variation affecting antigenic expression on the red blood cell surface in many populations is lacking. This deficit limits the ability to accurately type patients, especially as serological testing is not available for all described blood groups, and targeted genotyping panels may lack rare or population-specific variants. Here, we perform serological assays across 24 antigens and whole genome sequencing on 100 Omanis, a population underrepresented in genomic databases. We inferred blood group phenotypes using the most commonly typed genetic variants. The comparison of serological to inferred phenotypes resulted in an average concordance of 96.9%. Among the 22 discordances, we identify seven known variants in four blood groups that, to our knowledge, have not been previously reported in Omanis. Incorporating these variants for phenotype inference, concordance increases to 98.8%. Additionally, we describe five candidate variants in the Lewis, Lutheran, MNS, and P1 blood groups that may affect antigenic expression, although further functional confirmation is required. Notably, we identify several blood group alleles most common in African populations, likely introduced to Oman by gene flow over the last thousand years. These findings highlight the need to evaluate individual populations and their population history when considering variants to include in genotype panels for blood group typing. This research will inform future work in blood banks and transfusion services.

Yield of Cardiac Investigations in Patients Presenting with Acute Ischaemic Stroke: A single tertiary centre experience.

Objectives: Strokes are a major cause of morbidity and mortality. This study aimed to evaluate the effectiveness of routine cardiac investigations in identifying a cardioembolic aetiology for ischaemic strokes. Methods: This retrospective study involved patients who presented with a stroke to the Sultan Qaboos University Hospital, Muscat, Oman, between January and December 2019. Results: A total of 183 patients (mean age = 66.2 ± 13.5 years), the majority of which were male (n = 109, 59.6%), were included. The common risk factors included hypertension (74.9%), diabetes (61.7%) and hyperlipidaemia (54.6%). The middle cerebral artery was the most common artery affected, in 44 patients (24.0%). On admission, 14 (7.6%) patients were in atrial fibrillation (AF), while the rest were in sinus rhythm. The 24-hour electrocardiogram (ECG) Holter monitoring revealed no abnormalities in 135 patients. AF was observed in 15 (8.1%) patients (inclusive of the 14 who had AF on resting ECG). Furthermore, 32 (17.4%) patients had evidence of non-sustained atrial arrhythmia, and nine (4.9%) had non-sustained ventricular tachycardia. Frequent supraventricular ectopics (>30/hour) was noted on 30 patients (16.3%), while five (2.7%) patients had a high ventricular ectopic burden (>10% burden). No significant abnormalities were noted in the echocardiograms of the patients; however, 10 out of 132 (7.5%) patients presented a positive bubble echo. Enlarged left atria were found in 24 (13.1%) patients. Conclusion: The overall diagnostic yield of the abnormalities from routine cardiac testing for patients with stroke appears to be low. Targeted screening of patients with cryptogenic stroke, as suggested by newer guidelines, is recommended.

Business trends & challenges in Islamic FinTech: A systematic literature review.

Background: This systematic literature review (SLR) study is on Islamic financial technology (FinTech) business trends and challenges. It follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. This research identifies the gaps in Islamic FinTech, which require further studies. Moreover, it highlights the issues raised during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This study is based on the FinTech business model (BM) classifications by Lee & Shin and Imerman & Fabozzi. Furthermore, the set of challenges used in this study are adopted from research by Lee & Shin and Li & Xu. The Scopus database was used to collect data using nine keywords. Articles and review papers published between 2016 and 2022 were included. Studies that were not published in English, and those with no ranking journals were excluded. The results were presented using bibliometric analysis. Results: The results showed 36 articles discussing Islamic FinTech business trends and challenges, and most of these studies are conducted on FinTech crowdfunding vertical BM. By contrast, the most dominant horizontal BMs are FinTech regulation and FinTech funding BMs. The top challenge found in this study is the regulation management challenges. Moreover, there are remarkable dominating articles and reviews published in 2020 and 2021 discussing COVID-19. Conclusions: This study concluded that many horizontal BMs were not covered in Islamic FinTech, especially horizontal technology BMs. Investment, property and insurance BMs are examples of unavailable articles. Islamic FinTech is considered a promising field due to the size of the opportunities it presents, the available capital, and the great demand for banking and financial products that comply with the Sharia. This study will help the Islamic FinTech industry grow and predict the demand, and provide an alternative to conventional banking FinTech and further boost the technology progress in the financial industry.