Abstract
In our previous study, in which array CGH was used on 19 Lebanese ASD subjects and their parents, we identified rare copy number variants (CNVs) in 14 subjects. The five remaining subjects did not show any CNVs related to autism spectrum disorders (ASD). In the present complementary study, we applied whole-exome sequencing (WES), which allows the identification of rare genetic variations such as single nucleotide variations and small insertions/deletions, to the five negative CNV subjects. After stringent filtering of initial data on the five families, three novel genes potentially related to neurodevelopment were identified, including a de novo mutation in the MIS18BP1 gene. In addition, genes already known to be related to ASD contained sequence variations. Our findings outline the potential involvement of the novel de novo mutation in the MIS18BP1 gene in the genetic etiology and pathophysiology of ASD and highlights the genetic complexity of these disorders. Further studies with larger cohorts of subjects are needed to confirm these observations, and functional analyses need to be performed to understand the precise pathophysiology in these cases.
Highlights
According to the Diagnostic and Statistical Manual of Mental Disorders DSM-5, autism spectrum disorders (ASD) are extremely variable conditions characterized by impairments in reciprocal social communication and the use of restrictive and repetitive routines, typically manifesting before the age of 3 years [1] and affecting boys 4 times more than girls [2]
We reported a high percentage of copy number variants (CNVs) in 14 subjects
Afterwards, the families were invited to a meeting with our team in which we explained the different steps of the study
Summary
According to the Diagnostic and Statistical Manual of Mental Disorders DSM-5, autism spectrum disorders (ASD) are extremely variable conditions characterized by impairments in reciprocal social communication and the use of restrictive and repetitive routines, typically manifesting before the age of 3 years [1] and affecting boys 4 times more than girls [2]. For 2016, in the United States, the estimated ASD prevalence has gradually risen to affect 1 in every 54 children who are 8 years of age, according to a recently published report by the Centers for Disease Control and Prevention (CDC) [3]. Variations in multiple genes provide strong evidence of the involvement of genetic factors that explain most of ASD risk [5]. An important proportion of these genes encodes proteins implicated in synaptic function, ubiquitination, and chromatin remodeling [8]
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