Genomic architecture of autism spectrum disorder in Qatar: The BARAKA-Qatar Study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, and repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying ASD both in Qatar and the greater Middle East has been largely unexplored. Here, we describe the first genomic data release from the BARAKA-Qatar Study-a nationwide program building a broadly consented biorepository of individuals with ASD and their families available for sample and data sharing and multi-omics research. METHODS: In this first release, we present a comprehensive analysis of whole-genome sequencing (WGS) data of the first 100 families (372 individuals), investigating the genetic architecture, including single-nucleotide variants (SNVs), copy number variants (CNVs), tandem repeat expansions (TREs), as well as mitochondrial DNA variants (mtDNA) segregating with ASD in local families. RESULTS: Overall, we identify potentially pathogenic variants in known genes or regions in 27 out of 100 families (27%), of which 11 variants (40.7%) were classified as pathogenic or likely-pathogenic based on American College of Medical Genetics (ACMG) guidelines. Dominant variants, including de novo and inherited, contributed to 15 (55.6%) of these families, consisting of SNVs/indels (66.7%), CNVs (13.3%), TREs (13.3%), and mtDNA variants (6.7%). Moreover, homozygous variants were found in 7 families (25.9%), with a sixfold increase in homozygous burden in consanguineous versus non-consanguineous families (13.6% and 1.8%, respectively). Furthermore, 28 novel ASD candidate genes were identified in 20 families, 23 of which had recurrent hits in MSSNG and SSC cohorts. CONCLUSIONS: This study illustrates the value of ASD studies in under-represented populations and the importance of WGS as a comprehensive tool for establishing a molecular diagnosis for families with ASD. Moreover, it uncovers a significant role for recessive variation in ASD architecture in consanguineous settings and provides a unique resource of Middle Eastern genomes for future research to the global ASD community.

The Arabic Questionnaire for Psychotic Experiences in patients with psychotic disorders: a clinical validation.

BACKGROUND: Psychotic experiences are reported in the general population. The Questionnaire for Psychotic Experiences (QPE) was created to test the phenomenological features of these experiences and compare them with those reported in patients with psychiatric and other medical conditions. The aim of this study was to test the psychometric properties of the Arabic version of the QPE. METHODS: We recruited 50 patients with psychotic disorders from the Hamad Medical Hospital in Doha, Qatar. Patients underwent assessment over three sessions with trained interviewees using the Arabic versions of QPE, Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI), and the Global Assessment of Functioning Scale (GAF). Patients were also reassessed using the QPE and GAF after 14-days from the initial assessment in order to test for the stability of the scale. In this respect, this is the first study that assesses the test-retest reliability of the QPE. The psychometric properties including convergent validity, stability, and internal consistency met the benchmarked criteria. RESULTS: Results confirmed that the Arabic version of QPE accurately measured the experiences of patients that were also reported using the PANSS, an internationally accepted, well-established scale for measuring psychotic symptom severity. CONCLUSION: We propose the use of the QPE to describe the phenomenology of PEs across modalities in Arabic speaking communities.

Circulating Non-Coding RNAs as a Signature of Autism Spectrum Disorder Symptomatology.

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder that becomes apparent during early childhood development. The complexity of ASD makes clinically diagnosing the condition difficult. Consequently, by identifying the biomarkers associated with ASD severity and combining them with clinical diagnosis, one may better factionalize within the spectrum and devise more targeted therapeutic strategies. Currently, there are no reliable biomarkers that can be used for precise ASD diagnosis. Consequently, our pilot experimental cohort was subdivided into three groups: healthy controls, individuals those that express severe symptoms of ASD, and individuals that exhibit mild symptoms of ASD. Using next-generation sequencing, we were able to identify several circulating non-coding RNAs (cir-ncRNAs) in plasma. To the best of our knowledge, this study is the first to show that miRNAs, piRNAs, snoRNAs, Y-RNAs, tRNAs, and lncRNAs are stably expressed in plasma. Our data identify cir-ncRNAs that are specific to ASD. Furthermore, several of the identified cir-ncRNAs were explicitly associated with either the severe or mild groups. Hence, our findings suggest that cir-ncRNAs have the potential to be utilized as objective diagnostic biomarkers and clinical targets.

A chromosomal microdeletion of 15q in a female patient with epilepsy, ID, and autism spectrum disorder: a case report.

15q deletions have been described in association with intellectual disability and autism spectrum disorder (ASD). Previous reports have supported the role of 15q24 low copy repeats (LCRs) in mediating alternatively sized genomic rearrangements. Based on our reported finding of a 15q24 deletion coinciding with two LCR regions in a patient with epilepsy and ASD, we recommend that patients with 15q24 deletions be evaluated for ASD for early institution of therapy.