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 aut...
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AIMS Press
2024-11-01
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| Series: | AIMS Molecular Science |
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| Online Access: | https://www.aimspress.com/article/doi/10.3934/molsci.2024023 |
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| author | Rim Khelifi Afef Jelloul Houda Ajmi Wafa Slimani Sarra Dimassi Khouloud Rjiba Manel Dardour Moez Gribaa Ali Saad Soumaya Mougou-Zerelli |
| author_facet | Rim Khelifi Afef Jelloul Houda Ajmi Wafa Slimani Sarra Dimassi Khouloud Rjiba Manel Dardour Moez Gribaa Ali Saad Soumaya Mougou-Zerelli |
| author_sort | Rim Khelifi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ba2fb3c42adc40ef812e14f02d9d63c8 |
| institution | Kabale University |
| issn | 2372-0301 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | AIMS Press |
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| series | AIMS Molecular Science |
| spelling | doaj-art-ba2fb3c42adc40ef812e14f02d9d63c82025-01-24T01:33:38ZengAIMS PressAIMS Molecular Science2372-03012024-11-0111437939410.3934/molsci.2024023Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insightsRim Khelifi0Afef Jelloul1Houda Ajmi2Wafa Slimani3Sarra Dimassi4Khouloud Rjiba5Manel Dardour6Moez Gribaa7Ali Saad8Soumaya Mougou-Zerelli9Laboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaPasteur institute Tunis, TunisiaPaediatric Department, Sahloul University Hospital Sousse, TunisiaLaboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaLaboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaLaboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaPedopsychiatrist, private practice Sousse, TunisiaLaboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaLaboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaLaboratory of Cytogenetics, Molecular Genetics and Human Reproductive Biology CHU Farhat Hached Sousse, TunisiaIntroductionWilliams-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.https://www.aimspress.com/article/doi/10.3934/molsci.2024023cgh-arraywilliams beuren-syndromeautistic traitship1 |
| spellingShingle | Rim Khelifi Afef Jelloul Houda Ajmi Wafa Slimani Sarra Dimassi Khouloud Rjiba Manel Dardour Moez Gribaa Ali Saad Soumaya Mougou-Zerelli Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights AIMS Molecular Science cgh-array williams beuren-syndrome autistic traits hip1 |
| title | Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights |
| title_full | Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights |
| title_fullStr | Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights |
| title_full_unstemmed | Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights |
| title_short | Toward autism spectrum disorders and Williams-Beuren syndrome co-occurrence condition in Tunisian patients: Genetic insights |
| title_sort | toward autism spectrum disorders and williams beuren syndrome co occurrence condition in tunisian patients genetic insights |
| topic | cgh-array williams beuren-syndrome autistic traits hip1 |
| url | https://www.aimspress.com/article/doi/10.3934/molsci.2024023 |
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