Identification of the novel HLA-A*32:01:01:08 allele in a Saudi individual.

HLA-A*32:01:01:08 differs from HLA-A*32:01:01:01 by a single nucleotide substitution (G → A) at position 2200.

Identification of the novel HLA-B*51:230 allele in a Saudi individual.

One nucleotide replacement at codon 349 of HLA-B*51:01:01:01 results in a new allele, HLA-B*51:230.

ABO and Rh blood group genotypes in a cohort of Saudi stem cell donors.

The ABO and rhesus (Rh) blood group antigens are the most frequently studied genetic markers in a large group of people. Blood type frequencies vary in different racial/ethnic groups. Our objective was to investigate the distribution of the ABO and rhesus (Rh) blood groups by molecular typing method in a population of Saudi stem cell donors. Our data indicate that the most common blood group in our population is group O followed by group A then group B, and finally, the least common is group AB.

HLA class II polymorphism in Saudi patients with multiple sclerosis.

Several studies have investigated the association of different HLA antigens with multiple sclerosis (MS). However, only few studies have considered the association of high-resolution HLA type and MS with none yet from Saudi Arabia. The aim of this study was to investigate the association of HLA class II alleles with MS in the Saudi population. We used next-generation sequencing to investigate HLA association with MS. This study was conducted at King Abdulaziz Medical City in Riyadh, Saudi Arabia. We found that several HLA-DRB1 and DQB1 alleles were associated with MS. These alleles included HLA-DRB1*15:01 (odds ratio [OR]: 3.01; 95%, confidence interval [CI]: 1.68-5.54; P = .0001), HLA-DQB1*02:01 (OR: 1.76; 95% CI: 1.20-2.58; P = .0022), HLA-DQB1*06:02 (OR: 3.52; 95% CI: 1.87-6.86; P < .0001), and HLA-DQB1*06:03 (OR: 2.42; 95% CI: 1.16-5.25; P = 0.01). Interestingly, HLA-DRB1*15:01 was associated with increased risk of previous relapses. In addition, HLA-DRB1*15:01 and HLA-DQB1*06:02 were found to be associated with lower vitamin D levels. This study provides insights on the association of different HLA alleles with clinical characteristics and outcome of MS among Saudis. These insights can have future implications for the clinical management of MS based on the patient genetic profile.

Identification of the HLA-DQB1*06:123 allele in an unrelated stem cell donor from the Saudi Registry.

HLA-DQB1*06:123 differs from HLA-DQB1*06:29 by six nucleotide substitutions resulting in five amino acid changes.

Description of a novel HLA-DQB1 allele, HLA-DQB1*06:126, in the Saudi stem cell donor registry.

HLA-DQB1*06:126 differs from HLA-DQB1*06:02:01 by a nonsynonymous C to T substitution at nucleotide position 1621 in Exon 2.

Three new HLA-C alleles (HLA-C*14:02:13, HLA-C*15:72 and HLA-C*15:74) in Saudi bone marrow donors.

Three new HLA-C alleles were identified by sequence-based typing method (SBT) in donors for the Saudi Bone Marrow Donor Registry (SBMDR). HLA-C*14:02:13 differs from HLA-C*14:02:01 by a silent G to A substitution at nucleotide position 400 in exon 2, where lysine at position 66 remains unchanged. HLA-C*15:72 differs from HLA-C*15:22 by a nonsynonymous C to A substitution at nucleotide position 796 in exon 3, resulting in an amino acid change from phenylalanine to leucine at position 116. HLA-C*15:74 differs from HLA-C*15:08 by a nonsynonymous C to T substitution at nucleotide position 914 in exon 3, resulting in an amino acid change from arginine to tryptophan at position 156.

A novel HLA-DQ allele, HLA-DQB1*05:48, found in the Saudi Stem Cells Donor Registry.

The allele HLA-DQB1*05:48 differs from HLA-DQB1*05:01:01 by a non-synonymous T to C substitution at nucleotide position 1693 in exon 2.

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV).

BACKGROUND: Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU. FINDING: The three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement. INTERPRETATION: CNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed.

Two novel alleles HLA-A*02:433 and HLA-A*02:434 identified in Saudi bone marrow donors using sequence-based typing.

In this report, we present two novel HLA-A alleles: HLA-A*02:433 and HLA-A*02:434. These alleles were identified by sequence-based typing method (SBT), in two donors for the Saudi Bone Marrow Donor Registry (SBMDR). Allele A*02:433 is identical to A*02:05:01G except for a G to A substitution at nucleotide position 449 in exon 2. This substitution results in glycine to serine substitution at position 83. Whereas, allele A*02:434 is identical to A*02:01:01G except for a C to A substitution at nucleotide position 245 in exon 2, which results in phenylalanine to threonine substitution at position 15. The generation of both alleles appears to be the result of nucleotide point mutation involving 02:01:01 and 02:05:01.

Two novel alleles HLA-DRB1*11:150 and HLA-DRB1*14:145 identified in Saudi individuals.

Two new HLA- DRB1 alleles were identified by sequence-based typing method (SBT) in 1100 participants in the Saudi Stem Cell Donor Registry. HLA-DRB1*11:150 differs from HLA-DRB1*11:01:01G by a single C to A substitution at nucleotide position 5580 in exon 2, resulting in an amino acid change from alanine to glutamic acid at position 74. HLA-DRB1*14:145 differs from HLA-DRB1*14:04 by a C to G substitution at nucleotide position 5511 in exon 2, resulting in an amino acid change from threonine to arginine at position 51.

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in Saudis using next generation sequencing technique.

Next generation sequencing (NGS) is a promising technique that can reveal the entire gene sequences and to the highest possible resolution without any phase ambiguities. We have used this technique to investigate the frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 in a Saudi cohort of healthy individuals. We used NGS using the 454 genome sequence (GS) FLX System and Conexio assign atf 454 software to human leukocyte antigen (HLA) genotype eight class I and class II loci. A total of 158 healthy Saudi adults were analyzed. The most frequently observed allele for HLA-A was HLA-A*02:01:01:01 (13.6%); for HLA-B, HLA-B*50:01:01 (15.8%); for HLA-C, HLA-C*06:02:01:01 (18.7%); for HLA-DRB1, HLA-DRB1*07:01:01:01 (26.6%); and for HLA-DQB1, HLA-DQB1*02:01:01 (20.3%). The most common four loci haplotypes in the Saudi population were HLA-A*24:02:01:01-B*08:01:01-C*07:02:01:01-DRB1*03:01:01:01 and HLA-A*23:01:01-B*50:01:01-C*06:02:01:01-DRB1*07:01:01:01.. We have used a highly informative technique for HLA typing of a Saudi healthy cohort to establish allele and haplotype frequencies. These results should prove useful for population studies, disease associations and future planning of the unrelated bone marrow donor registry.

Pronase-free B-cell flow-cytometry crossmatch.

Detection of anti-class II antibodies by panel response assay (PRA) and flow cross-match techniques carries an important value in terms of graft function. Even low levels of pre-formed alloantibodies to HLA class II antigens represent a risk of rejection. We present here a method for blocking non-specific flow crossmatch reactions using pooled, heat-inactivated rabbit serum. This method shows very low background and minimal non-specific reactions. In addition, it avoids the use pronase enzyme that can non-specifically digest different cell surface proteins.

HLA class I and class II polymorphisms in Saudi patients with myasthenia gravis.

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. MG has been shown to be associated with many HLA antigens in different populations. Here we have analysed the frequency of HLA-A, B, DR and DQ in a group of Saudi MG patients and compared their results to a group of healthy controls. MG in Saudi patients is found to be associated with HLA-A*23, B*08, B*18, DRB1*16 and DRB1*13. The strongest association was with HLA-B*08, which was associated with young age at onset and female gender. Our results are in line with other published results from around the world and warrant fine mapping of the area using microsatellite to map the disease gene.

Integration of evidence based medicine into a medical curriculum.

The College of Medicine at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) was established in January 2004. The four-year curriculum was based on the Problem Based Learning (PBL) format and involved the web-based graduate medical program adopted from the University of Sydney, Australia. At KSAU-HS, one additional semester was added to the beginning of this curriculum to prepare the students in English language skills, PBL, Information Technology and Evidence Based Medicine (EBM). EBM is part of the Personal and Professional Development (PPD) theme of the medical curriculum and is integrated into each stage of the medical curriculum. These modifications of the University of Sydney curriculum are presented here as a model of EBM integration into a college of medicine curriculum.

Polymorphisms in the endothelial nitric oxide synthase gene are associated with Behçet's disease.

OBJECTIVE: Reduced plasma nitric oxide (NO) levels in Behçet's disease (BD) patients have been implicated in the development of the endothelial abnormalities and thrombotic complications occurring in these patients. This study investigated the association of the endothelial NO Synthase (eNOS) gene polymorphisms with BD. METHODS: A case-control study was carried out using 193 unrelated Turkish BD patients and 106 healthy controls. All individuals were genotyped by PCR for two single-nucleotide polymorphisms (SNPs): -786 T-->C in the promoter region and 894 G-->T in exon 7 (Glu298Asp). A variable number of tandem repeats (VNTR) polymorphism in intron 4 was also investigated. RESULTS: The VNTR polymorphism was associated with BD, detected by an increased frequency of the b allele (odds ratio = 1.9, P = 0.0069) and b/b genotype (odds ratio = 2.2, P = 0.002) in patients. After the stratification of cases according to the family history, a significant difference between familial cases and controls in the -786 SNP was observed, with an increase in the frequency of the T allele (odds ratio = 2.5, P = 0.0016) and T/T genotype (odds ratio = 2.5, P = 0.0085), and the association of the VNTR polymorphism with BD became stronger. The -786*T and VNTR*b alleles were in linkage disequilibrium (D' = 0.65, P <0.0001), and the number of individuals homozygous for the -786*T/VNTR*b haplotype was significantly increased in the patients. CONCLUSIONS: eNOS gene polymorphisms are associated with BD, which might contribute to the reduced NO activity observed in BD patients.