Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights

IntroductionWilliams-Beuren syndrome (WBS) is a rare genetic disorder characterized by congenital heart defects, dysmorphic features, intellectual delay, and a distinctive social behavioral profile. This highly recurrent and homogeneous phenotype has been curiously reported to be associated with autism spectrum disorders (ASD). Both genetic and environmental origins have been implicated. This study aimed to describe Tunisian patients associated with WBS and ASD and explore the underlying etiologies.MethodsThirty-one clinically suspected WBS were referred for genetic exploration. A comprehensive evaluation using karyotyping, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (array-CGH) was performed.ResultsAll patients were clinically diagnosed and confirmed to have WBS through karyotyping and FISH analysis. Notably, six patients with complex or atypical clinical presentations underwent array-CGH. Two of these patients presented with ASD. Array CGH showed microdeletions ranging from 1.4 to 1.7 Mb in the 7q11.2 region. Further analysis of the extended region deletion identified a gene closely located in the deleted region, the HIP1 gene, involved in the central nervous system trafficking protein.DiscussionThe recurrent deletion in WBS, as well as the mirror duplication, may contribute to ASD development in some cases, suggesting a potential involvement of the ASD genes pathway in this region. However, recessive genetic origins should also be considered, particularly in consanguineous families. Furthermore, our findings highlight the potential role of genetic factors and regulatory elements within the deleted region in modulating gene expression, notably the HIP1 gene. This underscores the implications of gene dosage and environmental factors in the broader WBS region, notably with language and social development.ConclusionThe presence of ASD in WBS patients emphasizes the need to investigate all WBS patients for autistic traits to establish a better genotype–phenotype correlation. We underline the utility of array-CGH as a valuable genetic diagnostic tool for characterizing WBS cases, and we shed light on the complex interplay of behavioral disorders in the 7q11.2 region rearrangements.