Abstract
Autism spectrum disorders (ASDs) are a group of neurodevelopmental-related disorders with a high genetic risk. Recently, chromatin remodeling factors have been found to be related to ASDs. SMARCA4 is such a catalytic subunit of the chromatin-remodeling complex. In this report, we identified seven novel missense variants in the SMARCA4 gene from eight pediatric patients. All eight patients had moderate to severe intellectual disability, and seven showed autistic/likely autistic features. Compared with the patients reported in the literature, our patients were less likely to show craniofacial or finger/toe anomalies. Our findings further supported that SMARCA4 is associated with ASDs. We suggest that individuals with the abovementioned phenotypes should consider genetic testing.
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Data Availability
Variants detected in this study were submitted to ClinVar with Accession Numbers VCV000816863, 000816863, 000816866 and Submission Number SUB10282901. The raw data are not publicly available due to ethical restrictions.
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Acknowledgments
We are very grateful to the patients’ families and the clinicians and our genetic laboratory teams who contributed to this study.
Funding
This study is funded by the Shanghai Sailing Program (18YF1402600), the National Natural Science Foundation of China (81741036, 81801462, 81974237) and the Research Project of Shanghai Municipal Health Commission (201940351).
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Dr. HW designed the study and revised the manuscript; Dr. YQ collected and interpreted the data, drafted the initial manuscript, and revised the manuscript; Dr. YZ, QX and XX oversaw the clinical genetic diagnosis and treated the patients; Miss YW and Mr. GL performed the sequence experiments; Mr. HC, Miss PZ and Miss SX interpreted the variants and drew the figures; Dr. WZ revised the manuscript; Dr. BW developed the laboratory, interpreted the data, and reviewed the manuscript; and all authors read and approved the manuscript.
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This study was approved by the ethics committees of Children's Hospital, Fudan University (2015-130 and 2016-235).
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Pretest counseling was performed, and informed consent for patients was obtained from at least one of their parents.
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Qian, Y., Zhou, Y., Wu, B. et al. Novel Variants of the SMARCA4 Gene Associated with Autistic Features Rather Than Typical Coffin-Siris Syndrome in Eight Chinese Pediatric Patients. J Autism Dev Disord 52, 5033–5041 (2022). https://doi.org/10.1007/s10803-021-05365-2
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DOI: https://doi.org/10.1007/s10803-021-05365-2