RASopathy
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.[1]
List of RASopathies
Known RASopathies include the following:[1][2]
- 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.[3] Generally, RASopathies increase the risk of developing cancers.[1][4] Neurodevelopmental or psychiatric disorders such as attention deficit hyperactivity disorder, autism spectrum disorder, and anxiety occur at higher rates in individuals with RASopathies.[5][6]
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:[2][7]
References
- ^ a b c Rauen KA (2022). "Defining RASopathy". Disease Models & Mechanisms. 15 (2). doi:10.1242/dmm.049344. PMC 8821523. PMID 35103797.
- ^ a b 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.
{{cite journal}}: 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.
{{cite journal}}: 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link)