Genetics of Neurodevelopmental Disorders

Our multidisciplinary research team aims at dentifying and validating novel genetic causes of neurodevelopmental disorders in human patients, taking advantage of clinically well characterized patient cohorts and of genomewide massive parallel sequencing approaches. We focus on patients with intellectual disability and autism, which may be present in combination with motor impairments and/or epilepsy. The identification of novel ID and autism gene provides the basis for future Precision Medicine practices within this vast group of disorders.

Funding Agency

FCT

Funding Agency

FCT

Project Reference

Project Members

Main Project Outcomes

S. Queirós, “Right ventricular segmentation in multi-view cardiac MRI using a unified U-net model”, in E. Puyol Antón et al. (eds) Statistical Atlases and Computational Models of the Heart. Multi-Disease, Multi-View, and Multi-Center Right Ventricular Segmentation in Cardiac MRI Challenge. STACOM 2021. Lecture Notes in Computer Science, vol 13131, pp. 287-295, Springer, Cham, 2022.

“Best Paper Award in the M&Ms-2 Challenge”, by M&Ms2 Challenge organizers and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society.

Main Project Outcomes

Monteiro-Fernandes, D., Charles, I., Guerreiro, S., Cunha-Garcia, D., Pereira-Sousa, J., Oliveira, S., Teixeira-Castro, A., Varney, M. A., Kleven, M. S., Newman-Tancredi, A., P Sheikh Abdala, A., Duarte-Silva, S., & Maciel, P. (2025). Rescue of Respiratory and Cognitive Impairments in Rett Syndrome Mice Using NLX-101, a Selective 5-HT1A Receptor Biased Agonist. Biomedicine & Pharmacotherapy, 186, 117989. https://doi.org/10.1016/j.biopha.2025.117989

Koko, M., Satterstrom, F. K., Autism Sequencing Consortium, APEX consortium, Warrier, V., & Martin, H. (2025). Contribution of Autosomal Rare and de novo Variants to Sex Differences in Autism. American Journal of Human Genetics, 112(3), 599–614. https://doi.org/10.1016/j.ajhg.2025.01.016

Fu, J. M., Satterstrom, F. K., Peng, M., Brand, H., Collins, R. L., Dong, S., Wamsley, B., Klei, L., Wang, L., Hao, S. P., Stevens, C. R., Cusick, C., Babadi, M., Banks, E., Collins, B., Dodge, S., Gabriel, S. B., Gauthier, L., Lee, S. K., Liang, L., Ljungdahl, A., Mahjani, B., Sloofman, L., Smirnov, A. N., Barbosa, M., Betancur, C., Brusco, A., Chung, B. H. Y., Cook, E. H., Cuccaro, M. L., Domenici, E., Ferrero, G. B., Gargus, J. J., Herman, G. E., Hertz-Picciotto, I., Maciel, P., Manoach, D. S., Passos-Bueno, M. R., Persico, A. M., Renieri, A., Sutcliffe, J. S., Tassone, F., Trabetti, E., Campos, G., Cardaropoli, S., Carli, D., Chan, M. C. Y., Fallerini, C., Giorgio, E., Girardi, A. C., Hansen-Kiss, E., Lee, S. L., Lintas, C., Ludena, Y., Nguyen, R., Pavinato, L., Pericak-Vance, M., Pessah, I. N., Schmidt, R. J., Smith, M., Costa, C. I. S., Trajkova, S., Wang, J. Y. T., Yu, M. H. C., Autism Sequencing Consortium (ASC), Broad Institute Center for Common Disease Genomics (Broad-CCDG), iPSYCH-BROAD Consortium,  Cutler, D. J., Rubeis, S. D., Buxbaum, J. D., Daly, M. J., Devlin, B., Roeder, K., Sanders, S. J., Talkowski, M. E. (2022). Rare Coding Variation Provides Insight into the Genetic Architecture and Phenotypic Context of Autism. Nature Genetics, 54(9), 1320-1331. https://doi.org/10.1038/s41588-022-01104-0

Da Silva, J. D., Oliveira, S., Pereira-Sousa, J., Teixeira-Castro, A., Costa, M. D., & Maciel, P. (2020). Loss of egli-1, the Caenorhabditis elegans Orthologue of a Downstream Target of SMN, Leads to Abnormalities in Sensorimotor Integration. Molecular Neurobiology, 57(3), 1553–1569. https://doi.org/10.1007/s12035-019-01833-0

Wen, J., Lopes, F., Soares, G., Farrell, S. A., Nelson, C., Qiao, Y., Martell, S., Badukke, C., Bessa, C., Ylstra, B., Lewis, S., Isoherranen, N., Maciel, P., & Rajcan-Separovic, E. (2013). Phenotypic and Functional Consequences of Haploinsufficiency of Genes from Exocyst and Retinoic Acid Pathway due to a Recurrent Microdeletion of 2p13.2. Orphanet Journal of Rare Diseases, 8, 100. https://doi.org/10.1186/1750-1172-8-100

Bessa, C., Maciel, P., & Rodrigues, A. J. (2013). Using C. elegans to Decipher the Cellular and Molecular Mechanisms Underlying Neurodevelopmental Disorders. Molecular Neurobiology, 48(3), 465–489. https://doi.org/10.1007/s12035-013-8434-6

Baptista, M. S., Duarte, C. B., & Maciel, P. (2012). Role of the Ubiquitin-Proteasome System in Nervous System Function and Disease: Using C. elegans as a Dissecting Tool. Cellular and Molecular Life Sciences, 69(16), 2691–2715. https://doi.org/10.1007/s00018-012-0946-0

Santos, M., Silva-Fernandes, A., Oliveira, P., Sousa, N., & Maciel, P. (2007). Evidence for Abnormal Early Development in a Mouse Model of Rett Syndrome. Genes, Brain, and Behavior, 6(3), 277–286. https://doi.org/10.1111/j.1601-183X.2006.00258.x

Santos, M., Summavielle, T., Teixeira-Castro, A., Silva-Fernandes, A., Duarte-Silva, S., Marques, F., Martins, L., Dierssen, M., Oliveira, P., Sousa, N., & Maciel, P. (2010). Monoamine Deficits in the Brain of Methyl-CpG Binding Protein 2 Null Mice Suggest the Involvement of the Cerebral Cortex in Early Stages of Rett Syndrome. Neuroscience, 170(2), 453–467. https://doi.org/10.1016/j.neuroscience.2010.07.010