Academic Journal
Biallelic ELMO3 mutations and loss of function for DOCK-mediated RAC1 activation result in intellectual disability
| العنوان: | Biallelic ELMO3 mutations and loss of function for DOCK-mediated RAC1 activation result in intellectual disability |
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| المؤلفون: | Tran, Viviane, Goyette, Marie-Anne, Martínez García, Mónica, Jiménez de Domingo, Ana, Fernández Mayoralas, Daniel Martín, Fernández Perrone, Ana Laura, Tirado, Pilar, Calleja Pérez, Beatriz, Álvarez de Andrés, Sara, Côté, Jean-François, Fernández Jaén, Alberto |
| سنة النشر: | 2022 |
| المجموعة: | Universidad Europea: ABACUS |
| مصطلحات موضوعية: | Trastorno del espectro autista, Deficiencia mental, Genética humana, Mutación |
| الوصف: | The engulfment and cell motility 3 (ELMO3) protein belongs to the ELMO-family of proteins. ELMO proteins form a tight complex with the DOCK1-5 guanine nucleotide exchange factors that regulate RAC1 spatiotemporal activation and signalling. DOCK proteins and RAC1 are known to have fundamental roles in central nervous system development. Here, we searched for homozygous or compound heterozygous mutations in the ELMO3 gene in 390 whole exomes sequenced in trio in individuals with neurodevelopmental disorders compatible with a genetic origin. We found a compound heterozygous mutation in ELMO3 (c.1153A>T, p.Ser385Cys and c.1009 G > A, p.Val337Ile) in a 5 year old male child with autism spectrum disorder (ASD) and developmental delay. These mutations did not interfere with the formation of an ELMO3/DOCK1 complex, but markedly impaired the ability of the complex to promote RAC1-GTP-loading. Consequently, cells expressing DOCK1 and either of the ELMO3 mutants displayed impaired migration and invasion. Collectively, our results suggest that biallelic loss-of-function mutations in ELMO3 may cause a developmental delay and provide new insight into the role of ELMO3 in neurodevelopmental as well as the pathological consequences of ELMO3 mutations. ; CIHR grant (PJT-153065) ; No data JCR 2021 ; 1.302 SJR (2021) Q1, 78/439 Biochemistry ; No data IDR 2021 ; UEM |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2154-1248 2154-1256 |
| Relation: | https://doi.org/10.1080/21541248.2021.1888557; Tran, V., Goyette, M. A., Martínez-García, M., Jiménez de Domingo, A., Fernández-Mayoralas, D. M., Fernández-Perrone, A. L., Tirado, P., Calleja-Pérez, B., Álvarez, S., Côté, J. F., & Fernández-Jaén, A. (2022). Biallelic ELMO3 mutations and loss of function for DOCK-mediated RAC1 activation result in intellectual disability. Small GTPases, 13(1), 48-55. https://doi.org/10.1080/21541248.2021.1888557; http://hdl.handle.net/11268/11364 |
| DOI: | 10.1080/21541248.2021.1888557 |
| الاتاحة: | http://hdl.handle.net/11268/11364 https://doi.org/10.1080/21541248.2021.1888557 |
| Rights: | openAccess |
| رقم الانضمام: | edsbas.CE629F8D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 21541248 21541256 |
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| DOI: | 10.1080/21541248.2021.1888557 |