The genetics of hyper IgE syndromes.

Hyper IgE syndromes (HIES) form a rare group of primary immunodeficiency disorders (PIDs) distinguished by persistent skin abscesses, dermatitis, allergies, and infections, in addition to their characteristic high serum IgE levels. Autosomal dominant (AD) and autosomal recessive (AR) genetic defects have been reported in HIES. From a clinical perspective, AD-HIES cases generally exhibit several non-immunologic features, including connective tissue, dental and skeletal abnormalities, whilst AR-HIES conditions have a higher incidence of neurologic complications and cutaneous viral infections.

Long-Term Outcomes and Survival in Patients Undergoing Multiple vs. Single Renal Artery Transplants: A Retrospective Cohort Study.

Introduction The incidence of end-stage renal disease (ESRD) is increasing, and strategies are needed to expand the available kidney donor pool. Urologists have not preferred multiple renal artery (MRA) grafts due to concerns about higher complication rates. This study aimed to compare graft and patient survival post-transplant, complications, and the time taken to reach the nadir creatinine levels.

Forging the path to precision medicine in Qatar: a public health perspective on pharmacogenomics initiatives.

Pharmacogenomics (PGx) is an important component of precision medicine that promises tailored treatment approaches based on an individual's genetic information. Exploring the initiatives in research that help to integrate PGx test into clinical setting, identifying the potential barriers and challenges as well as planning the future directions, are all important for fruitful PGx implementation in any population. Qatar serves as an exemplar case study for the Middle East, having a small native population compared to a diverse immigrant population, advanced healthcare system, national genome program, and several educational initiatives on PGx and precision medicine.

Identification of two novel autism genes, and , in Qatar simplex families through exome sequencing.

This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of and homozygous missense and splice variants.

Therapeutic targeting of the TPX2/TTK network in colorectal cancer.

Background: While the increased screening, changes in lifestyle, and recent advances in treatment regimen have decreased colorectal cancer (CRC) mortality, metastatic disease and recurrence remains a major clinical challenge. In the era of precision medicine, the identification of actionable novel therapeutic targets could ultimately offer an alternative treatment strategy for CRC.

Methods: RNA-Seq was conducted using the illumina platform, while bioinformatics analyses were conducted using CLC genomics workbench and iDEP.

Protegrin-2, a potential inhibitor for targeting SARS-CoV-2 main protease M.

Background: SARS-CoV-2 variants continue to spread throughout the world and cause waves of COVID-19 infections. It is important to find effective antiviral drugs to combat SARS-CoV-2 and its variants. The main protease (M) of SARS-CoV-2 is a promising therapeutic target due to its crucial role in viral replication and its conservation in all the variants.

Identification of a potential DNA methyltransferase (DNMT) inhibitor.

DNA methyltransferases (DNMTs) play an important role in the epigenetic regulation of gene expression through the methylation of DNA. Since hypermethylation and consequent suppression of tumor suppressor genes are associated with cancer development and progression, DNA hypomethylating agents (HMAs) such as DNMT inhibitors have been proposed for cancer therapy. Two nucleoside analogues approved for the treatment of hematological cancers, decitabine and azacytidine, have poor pharmacokinetic properties, and hence there is a critical need for identifying novel HMAs.

Artificial Intelligence for the Prediction and Early Diagnosis of Pancreatic Cancer: Scoping Review.

Background: Pancreatic cancer is the 12th most common cancer worldwide, with an overall survival rate of 4.9%. Early diagnosis of pancreatic cancer is essential for timely treatment and survival.

Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens.

Allelic diversity of human leukocyte antigen (HLA) class II genes may help maintain humoral immunity against infectious diseases. In this study, we investigated germline genetic variation in classical HLA class II genes and employed a systematic, unbiased approach to explore the relative contribution of this genetic variation in the antibody repertoire to various common pathogens. We leveraged a well-defined cohort of 800 adults representing the general Arab population in which genetic material is shared because of the high frequency of consanguineous unions.

Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly.

We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation.

A population study of clinically actionable genetic variation affecting drug response from the Middle East.

Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs.

Prescription Pattern and Off-Label Use of Antipsychotics in a Middle Eastern Population.

Understanding the prescription pattern of medications in a population can help reveal the potential usage scenarios, including off-label prescriptions, and the need for precision medicine implementation. Therefore, the aim of this study was to assess the prescription pattern and off-label use of antipsychotics in the Qatari population. We performed a cross-sectional study of Qatari patients who received antipsychotic prescriptions from the major healthcare providers in the country during the 2-year period between June 2018 and May 2020.

Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population.

Background: Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world. In Qatar, the incidence of G6PDD is estimated at around 5%; however, no study has investigated the genetic basis of G6PDD in the Qatari population yet.

Methods: In this study, we analyzed whole-genome sequencing data generated by the Qatar Genome Programme for 6045 Qatar Biobank participants, to identify G6PDD variants in the Qatari population.

A model based on cellular automata for investigating the impact of lockdown, migration and vaccination on COVID-19 dynamics.

Background And Objective: COVID-19 pandemic continues unabated due to the rapid spread of new mutant strains of the virus. Decentralized cluster containment is an efficient approach to manage the pandemic in the long term, without straining the healthcare system and economy. In this study, the objective is to forecast the peak and duration of COVID-19 spread in a cluster under different conditions, using a probabilistic cellular automata configuration designed to include the observed characteristics of the pandemic with appropriate neighbourhood schemes and transition rules.

Genome sequencing data analysis for rare disease gene discovery.

Rare diseases occur in a smaller proportion of the general population, which is variedly defined as less than 200 000 individuals (US) or in less than 1 in 2000 individuals (Europe). Although rare, they collectively make up to approximately 7000 different disorders, with majority having a genetic origin, and affect roughly 300 million people globally. Most of the patients and their families undergo a long and frustrating diagnostic odyssey.

Prescription Pattern of Antidepressants and the Potential for Personalized Medicine in the Qatari Population.

Studying the prescription pattern of medications will help in understanding potential unnecessary prescriptions, due to the trial-and-error method of prescribing, and the need for personalized medicine in a population. Therefore, in this study, our aim was to explore the prescribing pattern and off-label use of antidepressants in the Qatari population. We conducted a retrospective study of Qatari patients who received prescriptions for antidepressants from the major healthcare providers in Qatar, for a period of 24 months between June 2018 and May 2020.

First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes.

In 2019, we confirmed that the haploinsufficiency of CHD8 does indeed cause the novel syndromic neurodevelopmental disease we first discovered a dozen years before. Here, we report the first whole transcriptome RNAseq gene expression profiling for a patient with this new syndrome, as a preliminary exploration of potential pathophysiological mechanisms. We compared our patient transcriptome profile with that of all publicly available RNAseq datasets from human cellular models including neuronal progenitor cells, neurons and organoids.

Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling.

Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (MEFV) gene. Despite a typical clinical expression, many patients have either a single or no mutation in MEFV.

Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome.

Down syndrome (DS) is characterized by the occurrence of three copies of human chromosome 21 (HSA21). HSA21 contains a cluster of four interferon receptor (IFN-R) genes: IFNAR1, IFNAR2, IFNGR2, and IL10RB. DS patients often develop mucocutaneous infections and autoimmune diseases, mimicking patients with heterozygous gain-of-function (GOF) STAT1 mutations, which enhance cellular responses to three types of interferon (IFN).

The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar.

Background: Neonatal diabetes mellitus (NDM) is a rare condition that occurs within the first six months of life. Permanent NDM (PNDM) is caused by mutations in specific genes that are known for their expression at early and/or late stages of pancreatic beta- cell development, and are either involved in beta-cell survival, insulin processing, regulation, and release. The native population in Qatar continues to practice consanguineous marriages that lead to a high level of homozygosity.

Monoallelic expression in melanoma.

Background: Monoallelic expression (MAE) is a frequent genomic phenomenon in normal tissues, however its role in cancer is yet to be fully understood. MAE is defined as the expression of a gene that is restricted to one allele in the presence of a diploid heterozygous genome. Constitutive MAE occurs for imprinted genes, odorant receptors and random X inactivation.