Abstract
Autism spectrum disorder (ASD) is a highly heritable disease (~0.9) with a complex genetic etiology. It is initially characterized by altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in social interaction. Despite the large amount of studies described so far, the high clinical diversity affecting the autism phenotype remains poorly explained. Recent studies suggest that rare genomic variations, in particular copy number variation (CNV), may account for a significant proportion of the genetic basis of ASD. The use of disease-discordant monozygotic twins represents a powerful strategy to identify de novo and inherited CNV in the disorder. Here we present the results of a comparative genome hybridization (CGH) analysis with a pair of monozygotic twins affected of ASD with significant differences in their clinical manifestations that specially affect speech language impairment and communication skills. Array CGH was performed in three different tissues: blood, saliva, and hair follicle, in an attempt to identify germinal and somatic CNV regions that may explain these differences. Our results argue against a role of large CNV rearrangements as a molecular etiology of the observed differences. This forwards future research to explore de novo point mutation and epigenomic alterations as potential explanations of the observed clinical differences.
Highlights
Autism spectrum disorder (ASD) is characterized by deficits in social interaction and social communication, as well as by the presence of repetitive behaviors, restricted interests, and particular speech impairments
Highly penetrant copy number variation (CNV) or variants inherited in an autosomal recessive manner were detected in rare cases, previous results support the hypothesis that CNVs contribute to ASDs in association with other CNVs or point variants located elsewhere in the genome [5]
Normal karyotype analysis was observed in both twins and abnormalities at chromosome X affecting FMR1 locus methylation were discarded as an etiology for ASD
Summary
Autism spectrum disorder (ASD) is characterized by deficits in social interaction and social communication, as well as by the presence of repetitive behaviors, restricted interests, and particular speech impairments. We have taken advantage of array CGH to compare genomic DNA in three tissues: blood, saliva, and hair follicle, on a pair of discordant monozygotic twins with the aim to identify potential CNVs that could be associated with their differential ASD clinical outcomes. Subjects enrolled in the study were both 24-year-old male monozygotic twins denoted by TWO and TWX that were diagnosed with ASD at the age of 4.
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