Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping
Abstract Objective This study aimed to investigate the role of pathogenic copy number variations (CNVs) in neurodevelopmental impairments among children with corpus callosum abnormalities (CCAs). We focused primarily on SLC6A3 associated mechanisms and aimed to delineate genotype-phenotype correlati...
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BMC
2025-08-01
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| Series: | Molecular Cytogenetics |
| Online Access: | https://doi.org/10.1186/s13039-025-00725-4 |
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| author | Shan-yu Liu Wei Huang Hui-lin Ou Li Wang Dan-dan Wang Wei-he Tan Qin She |
| author_facet | Shan-yu Liu Wei Huang Hui-lin Ou Li Wang Dan-dan Wang Wei-he Tan Qin She |
| author_sort | Shan-yu Liu |
| collection | DOAJ |
| description | Abstract Objective This study aimed to investigate the role of pathogenic copy number variations (CNVs) in neurodevelopmental impairments among children with corpus callosum abnormalities (CCAs). We focused primarily on SLC6A3 associated mechanisms and aimed to delineate genotype-phenotype correlations in our cases. Methods From January 2021 to July 2023, 13 children with MRI-confirmed CCAs underwent chromosomal microarray analysis (CMA) for CNV detection. We performed bioinformatic analyses (Gene Ontology, STRING network) to identify neurodevelopmental genes within pathogenic CNVs, and clinical follow up assessed neurobehavioral outcomes. Results We identified pathogenic CNVs in 3/13 cases (23.08%). Specifically, Case 8 harbored a 43.05-Mb duplication (5p15.33p12) encompassing SLC6A3, a dopamine transporter gene linked to synaptic signaling. Interaction network analysis suggested that SLC6A3 was the most interconnected gene, providing evidence of its role in CCAs. Clinically, 84.6% of cases (11/13) exhibited psychomotor delay, while 15.4% of cases (2/13) developed seizure. Notably, we observed hearing impairment and psychomotor developmental delay in Case 8 with a SLC6A3 duplication, further suggesting dopaminergic dysregulation in callosal connectivity. Conclusion Our study suggests that SLC6A3 may represent a potential contributor to neurodevelopmental impairments in CCAs. Further, CMA-based CNV screening is critical for early intervention in high-risk children. These findings bridge genetic etiology with clinical phenotypes and offer insights into future targeted therapeutic strategies. |
| format | Article |
| id | doaj-art-e51c7454f5a5405e8e1ae01db107d032 |
| institution | Kabale University |
| issn | 1755-8166 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Molecular Cytogenetics |
| spelling | doaj-art-e51c7454f5a5405e8e1ae01db107d0322025-08-24T11:52:15ZengBMCMolecular Cytogenetics1755-81662025-08-011811810.1186/s13039-025-00725-4Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotypingShan-yu Liu0Wei Huang1Hui-lin Ou2Li Wang3Dan-dan Wang4Wei-he Tan5Qin She6Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Prenatal Diagnostic Center, the Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital)Abstract Objective This study aimed to investigate the role of pathogenic copy number variations (CNVs) in neurodevelopmental impairments among children with corpus callosum abnormalities (CCAs). We focused primarily on SLC6A3 associated mechanisms and aimed to delineate genotype-phenotype correlations in our cases. Methods From January 2021 to July 2023, 13 children with MRI-confirmed CCAs underwent chromosomal microarray analysis (CMA) for CNV detection. We performed bioinformatic analyses (Gene Ontology, STRING network) to identify neurodevelopmental genes within pathogenic CNVs, and clinical follow up assessed neurobehavioral outcomes. Results We identified pathogenic CNVs in 3/13 cases (23.08%). Specifically, Case 8 harbored a 43.05-Mb duplication (5p15.33p12) encompassing SLC6A3, a dopamine transporter gene linked to synaptic signaling. Interaction network analysis suggested that SLC6A3 was the most interconnected gene, providing evidence of its role in CCAs. Clinically, 84.6% of cases (11/13) exhibited psychomotor delay, while 15.4% of cases (2/13) developed seizure. Notably, we observed hearing impairment and psychomotor developmental delay in Case 8 with a SLC6A3 duplication, further suggesting dopaminergic dysregulation in callosal connectivity. Conclusion Our study suggests that SLC6A3 may represent a potential contributor to neurodevelopmental impairments in CCAs. Further, CMA-based CNV screening is critical for early intervention in high-risk children. These findings bridge genetic etiology with clinical phenotypes and offer insights into future targeted therapeutic strategies.https://doi.org/10.1186/s13039-025-00725-4 |
| spellingShingle | Shan-yu Liu Wei Huang Hui-lin Ou Li Wang Dan-dan Wang Wei-he Tan Qin She Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping Molecular Cytogenetics |
| title | Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping |
| title_full | Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping |
| title_fullStr | Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping |
| title_full_unstemmed | Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping |
| title_short | Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping |
| title_sort | potential role of slc6a3 in neurodevelopmental impairments associated with corpus callosum abnormalities insights from cnv analysis and clinical phenotyping |
| url | https://doi.org/10.1186/s13039-025-00725-4 |
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