The RASopathies are a group of developmental syndromes caused by germline mutations in genes belonging to the Ras/MAPK pathway. Common features include intellectual disability, congenital heart defects, skin abnormalities, and craniofacial abnormalities.
List of RASopathies
Known RASopathies include the following:
- Capillary malformation-AV malformation syndrome (CV-AVM)
- Cardiofaciocutaneous syndrome (CFC)
- Neurofibromatosis type I (NF1)
- Noonan syndrome (NS)
- Costello syndrome (CS)
- Legius syndrome, also known as NF1-like syndrome
- Noonan syndrome with multiple lentigines (NSML), formerly called LEOPARD syndrome
- SYNGAP1-related intellectual disability
Somatic mutations in the Ras/MAPK pathway can cause cancers and disorders such as RAS-associated autoimmune leukoproliferative disorder (RALD) or juvenile myelomonocytic leukemia (JMML). These syndromes may share some features with RASopathies but are not considered true RASopathies if caused by somatic mutation. Generally, RASopathies increase the risk of developing cancers. Neurodevelopmental or psychiatric disorders such as attention deficit hyperactivity disorder, autism spectrum disorder, and anxiety occur at higher rates in individuals with RASopathies.
Genetics
RASopathies are caused by germline mutations which result in overall activation of the Ras/MAPK pathway. Mutations in the following genes are associated with one or more types of RASopathy:
- HRAS
- KRAS
- NRAS
- RRAS
- RIT1
- NF1
- RASA1
- RASA2
- SYNGAP1
- SOS1
- SOS2
- CBL
- PTPN11
- BRAF
- RAF1
- MAP2K1
- MAP2K2
- MAP3K8
- SPRED1
- SPRY1
- MYST4
- LZTR1
- A2ML1
References
- ^ Rauen KA (2022). "Defining RASopathy". Disease Models & Mechanisms. 15 (2). doi:10.1242/dmm.049344. PMC 8821523. PMID 35103797.
- ^ Tidyman WE, Rauen KA (2016). "Pathogenetics of the RASopathies". Human Molecular Genetics. 25 (R2): R123 – R132. doi:10.1093/hmg/ddw191. PMC 6283265. PMID 27412009.
- Riller Q, Rieux-Laucat F (2021). "RASopathies: From germline mutations to somatic and multigenic diseases". Biomedical Journal. 44 (4): 422–432. doi:10.1016/j.bj.2021.06.004. PMC 8514848. PMID 34175492.
- Dunnett-Kane V, Burkitt-Wright E, Blackhall FH, Malliri A, Evans DG, Lindsay CR (2020). "Germline and sporadic cancers driven by the RAS pathway: parallels and contrasts". Annals of Oncology. 31 (7): 873–883. doi:10.1016/j.annonc.2020.03.291. PMC 7322396. PMID 32240795.
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: CS1 maint: multiple names: authors list (link) - Rai B, Naylor PE, Siqueiros-Sanchez M, Wintermark M, Raman MM, Jo B; et al. (2023). "Novel effects of Ras-MAPK pathogenic variants on the developing human brain and their link to gene expression and inhibition abilities". Translational Psychiatry. 13 (1): 245. doi:10.1038/s41398-023-02504-4. PMC 10322993. PMID 37407569.
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: CS1 maint: multiple names: authors list (link) - Zenker M (2022). "Clinical overview on RASopathies". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 190 (4): 414–424. doi:10.1002/ajmg.c.32015. PMID 36428239.
- Aoki Y, Niihori T, Inoue S, Matsubara Y (2016). "Recent advances in RASopathies". Journal of Human Genetics. 61 (1): 33–9. doi:10.1038/jhg.2015.114. PMID 26446362.
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: CS1 maint: multiple names: authors list (link)