Yield of array‐CGH analysis in Tunisian children with autism spectrum disorder

Abstract

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic underpinnings. Microarray‐based comparative genomic hybridization (aCGH) technology has been proposed as a first‐level test in the genetic diagnosis of ASD and of neurodevelopmental disorders in general. Methods We performed aCGH on 98 Tunisian children (83 boys and 15 girls) diagnosed with ASD according to DSM‐IV criteria. Results “Pathogenic” or “likely pathogenic” copy number variants (CNVs) were detected in 11 (11.2%) patients, CNVs of “uncertain clinical significance” in 26 (26.5%), “likely benign” or “benign” CNVs were found in 37 (37.8%) and 24 (24.5%) patients, respectively. Gene set enrichment analysis involving genes spanning rare “pathogenic,” “likely pathogenic,” or “uncertain clinical significance” CNVs, as well as SFARI database “autism genes” in common CNVs, detected eight neuronal Gene Ontology classes among the top 10 most significant, including synapse, neuron differentiation, synaptic signaling, neurogenesis, and others. Similar results were obtained performing g: Profiler analysis. Neither transcriptional regulation nor immune pathways reached significance. Conclusions aCGH confirms its sizable diagnostic yield in a novel sample of autistic children from North Africa. Recruitment of additional families is under way, to verify whether genetic contributions to ASD in the Tunisian population, differently from other ethnic groups, may involve primarily neuronal genes, more than transcriptional regulation and immune‐related pathways.

Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital

“…In this study, we used a previously validated and trained CMA platform [ 35 , 36 ] for the screening of apparently (under clinical geneticists’ supervision) non-syndromic ASD individuals, which allowed us to segregate up to 87% of individuals in the cohort or to classify CNVs in approximately 75% of the patients showing CNVs (see Figure 3 ). These rates are similar to or even higher than those previously published for global ASD in our country or nearby [ 19 , 23 , 24 , 30 , 32 , 34 ]. Regarding the quick segregation mentioned before, we were able to establish a statistically significant relationship between the size of the CNVs and their clinical classification (under ACM/AMP criteria) in primary ASD patients.…”

“…We found 28 cases carrying P/LP CNVs associated with apparently primary ASD (approximately 13% of the subjects) that were similar to previous reports in global ASD individuals [ 20 , 30 , 34 ] in the literature and slightly higher than other studies reported in our country [ 19 , 22 , 23 ], but is difficult to compare because many of the studies do not segregate between isolated and non-isolated ASD subjects. We also observed VUS variants in 26 of 212 cases (12.26%).…”

“…Therefore, few chromosomal regions have been identified for ASD individuals, with results ranging from 2.6% to 12.5% (average 8.65%) in Spain [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. CMA analysis has been widely used in ASD studies in many other countries, such as Canada, the United States, China, Saudi Arabia, Finland, Taiwan, Tunisia, Portugal, Italy, etc., with clearly significant results ranging from 2.7 to 22.5% [ 3 , 4 , 11 , 15 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”

A bibliometric analysis of autism spectrum disorder signaling pathways research in the past decade

“…These studies concentrate on various aspects of ASD in Tunisia, thoroughly investigating and analyzing multiple dimensions, including biology, cognition, psychosocial factors, and immunology. The research explores the impact of gut microbiota ( 59 ) and genomic variations ( 60 ) on patients, elucidating challenges in cognitive abilities ( 61 ), emotional recognition ( 62 ), and familial issues ( 63 ). Furthermore, investigations into immunological characteristics contribute to comprehending the pathological mechanisms of autism ( 64 ).…”

A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD

“…CNVs were found in 90% of the 333 CMAs analysed, and 38 CNVs interpreted as pathogenic were detected in 35 cases with ASD, resulting in a diagnostic yield of 10%, lower than the diagnostic rate for the whole cohort (17%), but within the range of 8 to 22% cited in the literature for other ASD cohorts 16,70,[73][74][75][76][77][78][79][80][81][82][83][84][85] . And without the ASD cases, the diagnostic rate of the cohort increases to 20%.…”