Dysregulation of long non-coding RNA gene expression pathways in monocytes of type 2 diabetes patients with cardiovascular disease.

Background: Monocytes play a central role in the pathophysiology of cardiovascular complications in type 2 diabetes (T2D) patients through different mechanisms. We investigated diabetes-induced changes in lncRNA genes from T2D patients with cardiovascular disease (CVD), long-duration diabetes, and poor glycemic control.

Methods: We performed paired-end RNA sequencing of monocytes from 37 non-diabetes controls and 120 patients with T2D, of whom 86 had either macro or microvascular disease or both.

DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome.

Background: COVID-19 infections could be complicated by acute respiratory distress syndrome (ARDS), increasing mortality risk. We sought to assess the methylome of peripheral blood mononuclear cells in COVID-19 with ARDS.

Methods: We recruited 100 COVID-19 patients with ARDS under mechanical ventilation and 33 non-COVID-19 controls between April and July 2020.

Altered Circulating microRNAs in Patients with Diabetic Neuropathy and Corneal Nerve Loss: A Pilot Study.

An alteration in circulating miRNAs may have important diagnostic and therapeutic relevance in diabetic neuropathy. Patients with type 2 diabetes mellitus (T2DM) underwent an assessment of neuropathic symptoms using Douleur Neuropathique 4 (DN4), the vibration perception threshold (VPT) using a Neurothesiometer, sudomotor function using the Sudoscan, corneal nerve morphology using corneal confocal microscopy (CCM) and circulating miRNAs using high-throughput miRNA expression profiling. Patients with T2DM, with (n = 9) and without (n = 7) significant corneal nerve loss were comparable in age, gender, diabetes duration, BMI, HbA1c, eGFR, blood pressure, and lipid profile.

Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction.

Background: Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD).

Methods: A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS).

The QChip1 knowledgebase and microarray for precision medicine in Qatar.

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 10 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs.

Novel mutation in microvillous inclusion disease of Syrian ancestry.

Microvillus inclusion disease (MVID) is a rare autosomal recessive condition characterized by a lack of microvilli on the surface of enterocytes, resulting in severe, life-threatening diarrhea that could lead to mortality within the first year of life. We identify two unrelated families, each with one child presenting with severe MVID from birth. Using trio whole-exome sequencing, we observed that the two families share a novel nonsense variant (Glu1589*) in the gene, a type Vb myosin motor protein in which rare damaging mutations were previously described to cause MVID.

Metabolic and Metabo-Clinical Signatures of Type 2 Diabetes, Obesity, Retinopathy, and Dyslipidemia.

Macro- and microvascular complications of type 2 diabetes (T2D), obesity, and dyslipidemia share common metabolic pathways. In this study, using a total of 1,300 metabolites from 996 Qatari adults (57% with T2D) and 1,159 metabolites from an independent cohort of 2,618 individuals from the Qatar BioBank (11% with T2D), we identified 373 metabolites associated with T2D, obesity, retinopathy, dyslipidemia, and lipoprotein levels, 161 of which were novel. Novel metabolites included phospholipids, sphingolipids, lysolipids, fatty acids, dipeptides, and metabolites of the urea cycle and xanthine, steroid, and glutathione metabolism.

A Novel STK4 Mutation Impairs T Cell Immunity Through Dysregulation of Cytokine-Induced Adhesion and Chemotaxis Genes.

Purpose: Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent to which immune signaling and host defense are impaired is unclear. We assessed the functional consequences of a novel, homozygous nonsense STK4 mutation (NM_006282.2:c.

Association of vitamin D and its metabolites in patients with and without type 2 diabetes and their relationship to diabetes complications.

Background: Epidemiological studies have suggested that vitamin D deficiency is associated with the development of type 2 diabetes (T2DM) and is related to diabetes complications. This study was undertaken to determine the relationship between diabetes complications and cardiovascular risk factors with vitamin D and its metabolites: 1,25-dihydroxyvitamin D (1,25(OH)D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)D); and 25-hydroxy-3epi-vitamin D (3epi25(OH)D).

Methods: 750 Qatari subjects, 460 (61.

Qatari Genotype May Contribute to Complications in Type 2 Diabetes.

Objective: There is increasing evidence of a strong genetic component in type 2 diabetes (T2DM) that may contribute to diabetes complications. Given the high prevalence of diabetes with its associated complications in the Middle East, we sought to determine if the genotype within a Middle East population may be contributory. Therefore, three genotype-based Qatari ancestral groups, Q1 Arab Bedouin, Q2 Asian/Persian, and Q3 sub-Saharan African, with a fourth admixed group were correlated with T2DM prevalence and its complications to determine if they differed between the 4 Qatari ancestries, particularly for the SLMAP allele-associated diabetic retinopathy.

Association of vitamin D and D with type 2 diabetes complications.

Aims: Vitamin D measurement is a composite of vitamin D (25(OH)D) and D (25(OH)D) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D supplements. This study was undertaken to determine if vitamin D and D levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D and vitamin D levels in subjects with T2DM METHODS: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D and D were measured by LC-MS/MS analysis.

Association of Differing Qatari Genotypes with Vitamin D Metabolites.

Objective: Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation.

Methods: 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays.

Point of Care Exome Sequencing Reveals Allelic and Phenotypic Heterogeneity Underlying Mendelian disease in Qatar.

The effectiveness of next generation sequencing at solving genetic disease has motivated the rapid adoption of this technology into clinical practice around the world. In this study, we use whole exome sequencing (WES) to assess 48 patients with Mendelian disease from 30 serial families as part of the "Qatar Mendelian Disease pilot program" - a coordinated multi-center effort to build capacity and clinical expertise in genetic medicine in Qatar. By enrolling whole families (parents plus available siblings), we demonstrate significantly improved discriminatory power for candidate variant identification over trios for both de novo and recessive inheritance patterns.

Exome sequencing-based identification of novel type 2 diabetes risk allele loci in the Qatari population.

Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and lifestyle factors. To date, the majority of genetic studies of T2D have been in populations of European and Asian descent. The focus of this study is on genetic variations underlying T2D in Qataris, a population with one of the highest incidences of T2D worldwide.

Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot.

Aim: Charcot foot (CF) is a rare complication of Type 2 diabetes (T2D).

Materials & Methods: We assessed circulating miRNAs in 17 patients with T2D and acute CF (G1), 17 patients with T2D (G2) and equivalent neuropathy and 17 patients with T2D without neuropathy (G3) using the high-throughput miRNA expression profiling.

Results: 51 significantly deregulated miRNAs were identified in G1 versus G2, 37 in G1 versus G3 and 64 in G2 versus G3.

Point-of-care whole-exome sequencing of idiopathic male infertility.

Purpose: Nonobstructive azoospermia (NOA) affects 1% of the male population; however, despite state-of-the-art clinical assessment, for most patients the cause is unknown. We capitalized on an analysis of multiplex families in the Middle East to identify highly penetrant genetic causes.

Methods: We used whole-exome sequencing (WES) in 8 consanguineous families and combined newly discovered genes with previously reported ones to create a NOA gene panel, which was used to identify additional variants in 75 unrelated idiopathic NOA subjects and 74 fertile controls.

A systematic review on the genetics of male infertility in the era of next-generation sequencing.

Objectives: To identify the role of next-generation sequencing (NGS) in male infertility, as advances in NGS technologies have contributed to the identification of novel genes responsible for a wide variety of human conditions and recently has been applied to male infertility, allowing new genetic factors to be discovered.

Materials And Methods: PubMed was searched for combinations of the following terms: 'exome', 'genome', 'panel', 'sequencing', 'whole-exome sequencing', 'whole-genome sequencing', 'next-generation sequencing', 'azoospermia', 'oligospermia', 'asthenospermia', 'teratospermia', 'spermatogenesis', and 'male infertility', to identify studies in which NGS technologies were used to discover variants causing male infertility.

Results: Altogether, 23 studies were found in which the primary mode of variant discovery was an NGS-based technology.

Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population.

Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human metabolic individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for a highly consanguineous Middle Eastern population, we discover 21 common variant and 12 functional rare variant mQTLs, of which 45% are novel altogether. We fine-map 10 common variant mQTLs to new metabolite ratio associations, and 11 common variant mQTLs to putative protein-altering variants.

Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups.

Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype.

Background: Ligase IV syndrome, a hereditary disease associated with compromised DNA damage response mechanisms, and Urofacial syndrome, caused by an impairment of neural cell signaling, are both rare genetic disorders, whose reports in literature are limited. We describe the first case combining both disorders in a specific phenotype.

Case Presentation: We report a case of a 7-year old girl presenting with a complex phenotype characterized by multiple congenital abnormalities and dysmorphic features, microcephaly, short stature, combined immunodeficiency and severe vesicoureteral reflux.

Correction: Type 2 Diabetes Risk Allele Loci in the Qatari Population.

[This corrects the article DOI: 10.1371/journal.pone.

The Qatar genome: a population-specific tool for precision medicine in the Middle East.

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population.

Type 2 Diabetes Risk Allele Loci in the Qatari Population.

Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians.

Methods: All subjects were ≥3 generation Qataris.