{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T17:14:04Z","timestamp":1769706844841,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["PNRR-MR1-2022-12375648"],"award-info":[{"award-number":["PNRR-MR1-2022-12375648"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hypoxic-ischemic brain damage presents a significant neurological challenge, often manifesting during the perinatal period. Specifically, periventricular leukomalacia (PVL) is emerging as a notable contributor to cerebral palsy and intellectual disabilities. It compromises cerebral microcirculation, resulting in insufficient oxygen or blood flow to the periventricular region of the brain. As widely documented, these pathological conditions can be caused by several factors encompassing preterm birth (4\u20135% of the total cases), as well single cotwin abortion and genetic variants such as those associated with GTPase pathways. Whole exome sequencing (WES) analysis identified a de novo causative variant within the pleckstrin homology domain-containing family G member 1 (PLEKHG1) gene in a patient presenting with PVL. The PLEKHG1 gene is ubiquitously expressed, showing high expression patterns in brain tissues. PLEKHG1 is part of a family of Rho guanine nucleotide exchange factors, and the protein is essential for cell division control protein 42 (CDC42) activation in the GTPase pathway. CDC42 is a key small GTPase of the Rho-subfamily, regulating various cellular functions such as cell morphology, migration, endocytosis, and cell cycle progression. The molecular mechanism involving PLEKHG1 and CDC42 has an intriguing role in the reorientation of cells in the vascular endothelium, thus suggesting that disruption responses to mechanical stress in endothelial cells may be involved in the formation of white matter lesions. Significantly, CDC42 association with white matter abnormalities is underscored by its MIM phenotype number. In contrast, although PLEKHG1 has been recently associated with patients showing white matter hyperintensities, it currently lacks a MIM phenotype number. Additionally, in silico analyses classified the identified variant as pathogenic. Although the patient was born prematurely and subsequently to dichorionic gestation, during which its cotwin died, we suggest that the variant described can strongly contribute to PVL. The aim of the current study is to establish a plausible association between the PLEKHG1 gene and PVL.<\/jats:p>","DOI":"10.3390\/genes15081096","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:13:48Z","timestamp":1724145228000},"page":"1096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PLEKHG1: New Potential Candidate Gene for Periventricular White Matter Abnormalities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-8223","authenticated-orcid":false,"given":"Francesco","family":"Cal\u00ec","sequence":"first","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-8510","authenticated-orcid":false,"given":"Mirella","family":"Vinci","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-9991","authenticated-orcid":false,"given":"Simone","family":"Treccarichi","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-612X","authenticated-orcid":false,"given":"Carla","family":"Papa","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-2844","authenticated-orcid":false,"given":"Angelo","family":"Gloria","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-3365","authenticated-orcid":false,"given":"Antonino","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Federico","sequence":"additional","affiliation":[{"name":"Department Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6285-9692","authenticated-orcid":false,"given":"Girolamo Aurelio","family":"Vitello","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Gennaro","family":"Nicotera","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Human Pathology of the Adult and Developmental Age, \u201cGaetano Barresi\u201d University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Di Rosa","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Human Pathology of the Adult and Developmental Age, \u201cGaetano Barresi\u201d University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0121-3396","authenticated-orcid":false,"given":"Luigi","family":"Vetri","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-5823","authenticated-orcid":false,"given":"Salvatore","family":"Saccone","sequence":"additional","affiliation":[{"name":"Department Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0414-1359","authenticated-orcid":false,"given":"Maurizio","family":"Elia","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3174\/ajnr.A0534","article-title":"Diffusion Tensor Imaging in Children with Periventricular Leukomalacia: Variability of Injuries to White Matter Tracts","volume":"28","author":"Nagae","year":"2007","journal-title":"Am. J. Neuroradiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pediatrneurol.2017.05.013","article-title":"Confusions in Nomenclature: \u201cPeriventricular Leukomalacia\u201d and \u201cWhite Matter Injury\u201d\u2014Identical, Distinct, or Overlapping?","volume":"73","author":"Volpe","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1203\/00006450-200111000-00003","article-title":"Neurobiology of Periventricular Leukomalacia in the Premature Infant","volume":"50","author":"Volpe","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2350\/06-01-0024.1","article-title":"Periventricular Leukomalacia: Overview and Recent Findings","volume":"9","author":"Folkerth","year":"2006","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1001\/archneur.65.10.1291","article-title":"Progress in Periventricular Leukomalacia","volume":"65","author":"Deng","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/08830738211026052","article-title":"Neuroradiological Mimics of Periventricular Leukomalacia","volume":"37","author":"Reddy","year":"2022","journal-title":"J. Child Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113600","DOI":"10.1016\/j.jpeds.2023.113600","article-title":"The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-Based Cohort Study","volume":"262","author":"Pascal","year":"2023","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1002\/hbm.22950","article-title":"Long Term Motor Function after Neonatal Stroke: Lesion Localization above All","volume":"36","author":"Dinomais","year":"2015","journal-title":"Hum. Brain Mapp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1017\/S0033291709991656","article-title":"Localization of White-Matter Lesions and Effect of Vascular Risk Factors in Late-Onset Major Depression","volume":"40","author":"Dalby","year":"2010","journal-title":"Psychol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1212\/WNL.0000000000006936","article-title":"The Emerging Genetic Landscape of Cerebral White Matter Hyperintensities","volume":"92","author":"Fornage","year":"2019","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0169-328X(02)00413-8","article-title":"Developmental Changes in Expression of Small GTPase RhoG MRNA in the Rat Brain","volume":"106","author":"Ishikawa","year":"2002","journal-title":"Mol. Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/glia.23548","article-title":"The Guanine Nucleotide Exchange Factor Vav3 Modulates Oligodendrocyte Precursor Differentiation and Supports Remyelination in White Matter Lesions","volume":"67","author":"Ulc","year":"2019","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108560","DOI":"10.1016\/j.celrep.2020.108560","article-title":"QUAKING Regulates Microexon Alternative Splicing of the Rho GTPase Pathway and Controls Microglia Homeostasis","volume":"33","author":"Lee","year":"2020","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Abiko, H., Fujiwara, S., Ohashi, K., Hiatari, R., Mashiko, T., Sakamoto, N., Sato, M., and Mizuno, K. Rho-Guanine Nucleotide Exchange Factors Involved in Cyclic Stretch-Induced Reorientation of Vascular Endothelial Cells. J. Cell Sci., 2015.","DOI":"10.1242\/jcs.157503"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nakano, S., Nishikawa, M., Kobayashi, T., Harlin, E.W., Ito, T., Sato, K., Sugiyama, T., Yamakawa, H., Nagase, T., and Ueda, H. (2022). The Rho Guanine Nucleotide Exchange Factor PLEKHG1 Is Activated by Interaction with and Phosphorylation by Src Family Kinase Member FYN. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101579"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1080\/21541248.2019.1658509","article-title":"Identification of Guanine Nucleotide Exchange Factors That Increase Cdc42 Activity in Primary Human Endothelial Cells","volume":"12","author":"Reinhard","year":"2021","journal-title":"Small GTPases"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e749","DOI":"10.1212\/WNL.0000000000006952","article-title":"Genetic Variation in PLEKHG1 Is Associated with White Matter Hyperintensities (n = 11,226)","volume":"92","author":"Traylor","year":"2019","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1161\/HYPERTENSIONAHA.117.10688","article-title":"Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1","volume":"72","author":"Gray","year":"2018","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0165-022X(92)90014-2","article-title":"A Non-Organic and Non-Enzymatic Extraction Method Gives Higher Yields of Genomic DNA from Whole-Blood Samples than Do Nine Other Methods Tested","volume":"25","author":"Lahiri","year":"1992","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Treccarichi, S., Failla, P., Vinci, M., Musumeci, A., Gloria, A., Vasta, A., Calabrese, G., Papa, C., Federico, C., and Saccone, S. (2024). UNC5C: Novel Gene Associated with Psychiatric Disorders Impacts Dysregulation of Axon Guidance Pathways. Genes, 15.","DOI":"10.3390\/genes15030306"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Vinci, M., Costanza, C., Galati Rando, R., Treccarichi, S., Saccone, S., Carotenuto, M., Roccella, M., Cal\u00ec, F., Elia, M., and Vetri, L. (2023). STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216436"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00414-001-0272-9","article-title":"DXYS156: A Multi-Purpose Short Tandem Repeat Locus for Determination of Sex, Paternal and Maternal Geographic Origins and DNA Fingerprinting","volume":"116","author":"Forster","year":"2002","journal-title":"Int. J. Legal Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W545","DOI":"10.1093\/nar\/gky471","article-title":"VarAFT: A Variant Annotation and Filtration System for Human next Generation Sequencing Data","volume":"46","author":"Desvignes","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The Human Genomic Variant Search Engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/prot.20810","article-title":"Prediction of Protein Stability Changes for Single-site Mutations Using Support Vector Machines","volume":"62","author":"Cheng","year":"2006","journal-title":"Proteins: Struct. Funct. Bioinform."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bell, E.W., Schwartz, J.H., Freddolino, P.L., and Zhang, Y. (2022). PEPPI: Whole-Proteome Protein-Protein Interaction Prediction through Structure and Sequence Similarity, Functional Association, and Machine Learning. J. Mol. Biol., 434.","DOI":"10.1016\/j.jmb.2022.167530"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jmoldx.2011.09.001","article-title":"Extensive Molecular Analysis of Patients Bearing CFTR-Related Disorders","volume":"14","author":"Amato","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jaci.2022.06.009","article-title":"Clinical Exome Sequencing of 1000 Families with Complex Immune Phenotypes: Toward Comprehensive Genomic Evaluations","volume":"150","author":"Similuk","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(00)02215-7","article-title":"Consequences of In-Utero Death in a Twin Pregnancy","volume":"355","author":"Pharoah","year":"2000","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/j.1471-0528.2006.01027.x","article-title":"Prognosis for the Co-twin Following Single-twin Death: A Systematic Review","volume":"113","author":"Ong","year":"2006","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/s41372-018-0190-z","article-title":"Comparison of Neurodevelopmental Outcomes between Monochorionic and Dichorionic Twins with Birth Weight \u2264 1500\u2009g in Japan: A Register-Based Cohort Study","volume":"38","author":"Ichinomiya","year":"2018","journal-title":"J. Perinatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"41.e1","DOI":"10.1016\/j.ajog.2009.02.003","article-title":"The Risk of Cerebral Palsy in Survivors of Multiple Pregnancies with Cofetal Loss or Death","volume":"201","author":"Taylor","year":"2009","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hack, K.E.A., Koopman-Esseboom, C., Derks, J.B., Elias, S.G., de Kleine, M.J.K., Baerts, W., Go, A.T.J.I., Schaap, A.H.P., van der Hoeven, M.A.H.B.M., and Eggink, A.J. (2009). Long-Term Neurodevelopmental Outcome of Monochorionic and Matched Dichorionic Twins. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006815"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1080\/00016340802503039","article-title":"Risk Factors for Periventricular Leukomalacia","volume":"88","author":"Hatzidaki","year":"2009","journal-title":"Acta Obs. Gynecol Scand"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gotardo, J.W., de Volkmer, N.F.V., Stangler, G.P., Dornelles, A.D., de Athayde Bohrer, B.B., and Carvalho, C.G. (2019). Impact of Peri-Intraventricular Haemorrhage and Periventricular Leukomalacia in the Neurodevelopment of Preterms: A Systematic Review and Meta-Analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223427"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S1474-4422(08)70294-1","article-title":"Brain Injury in Premature Infants: A Complex Amalgam of Destructive and Developmental Disturbances","volume":"8","author":"Volpe","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1046\/j.1440-1789.2002.00438.x","article-title":"Periventricular Leukomalacia, Inflammation and White Matter Lesions within the Developing Nervous System","volume":"22","author":"Rezaie","year":"2002","journal-title":"Neuropathology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/ana.22612","article-title":"Neuron Deficit in the White Matter and Subplate in Periventricular Leukomalacia","volume":"71","author":"Kinney","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.clml.2013.02.012","article-title":"Microarray Demonstrates Different Gene Expression Profiling Signatures Between Waldenstr\u00f6m Macroglobulinemia and IgM Monoclonal Gammopathy of Undetermined Significance","volume":"13","author":"Trojani","year":"2013","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jpeds.2005.06.043","article-title":"Cystic Fibrosis Birth Rates in Canada: A Decreasing Trend since the Onset of Genetic Testing","volume":"147","author":"Dupuis","year":"2005","journal-title":"J. Pediatr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/s41436-020-01073-x","article-title":"Cystic Fibrosis\u2013Related Diabetes Onset Can Be Predicted Using Biomarkers Measured at Birth","volume":"23","author":"Lin","year":"2021","journal-title":"Genet. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0014-5793(01)03310-5","article-title":"Signaling to the Rho GTPases: Networking with the DH Domain","volume":"513","author":"Hoffman","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrm1587","article-title":"GEF Means Go: Turning on RHO GTPases with Guanine Nucleotide-Exchange Factors","volume":"6","author":"Rossman","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1074\/jbc.M112.429746","article-title":"Deciphering the Molecular and Functional Basis of Dbl Family Proteins","volume":"288","author":"Jaiswal","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18202","DOI":"10.1074\/jbc.M111.226431","article-title":"Mechanistic Insights into Specificity, Activity, and Regulatory Elements of the Regulator of G-Protein Signaling (RGS)-Containing Rho-Specific Guanine Nucleotide Exchange Factors (GEFs) P115, PDZ-RhoGEF (PRG), and Leukemia-Associated RhoGEF (LARG)","volume":"286","author":"Jaiswal","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mosaddeghzadeh, N., and Ahmadian, M.R. (2021). The RHO Family GTPases: Mechanisms of Regulation and Signaling. Cells, 10.","DOI":"10.3390\/cells10071831"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/cbic.200300781","article-title":"Coiled Coil Domains: Stability, Specificity, and Biological Implications","volume":"5","author":"Mason","year":"2004","journal-title":"ChemBioChem"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.sbi.2008.04.008","article-title":"Structural Specificity in Coiled-Coil Interactions","volume":"18","author":"Grigoryan","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.jmb.2012.11.041","article-title":"Impact of Mutations on the Allosteric Conformational Equilibrium","volume":"425","author":"Weinkam","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"25445","DOI":"10.1073\/pnas.2002613117","article-title":"Functional Plasticity and Evolutionary Adaptation of Allosteric Regulation","volume":"117","author":"Leander","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e7025","DOI":"10.7717\/peerj.7025","article-title":"Discovery of Plasma Messenger RNA as Novel Biomarker for Gastric Cancer Identified through Bioinformatics Analysis and Clinical Validation","volume":"7","author":"Cao","year":"2019","journal-title":"PeerJ"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1038\/s41467-022-34514-z","article-title":"Epigenetic Alterations of Repeated Relapses in Patient-Matched Childhood Ependymomas","volume":"13","author":"Zhao","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajhg.2017.12.015","article-title":"Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes","volume":"102","author":"Martinelli","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1212\/01.wnl.0000224754.63593.c4","article-title":"Molecular Mechanisms of Cell Death in Periventricular Leukomalacia","volume":"67","author":"Kadhim","year":"2006","journal-title":"Neurology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pneurobio.2009.01.003","article-title":"Periventricular White Matter Damage in the Hypoxic Neonatal Brain: Role of Microglial Cells","volume":"87","author":"Kaur","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_57","first-page":"217","article-title":"Impacts of Erythropoietin on Vascular Endothelial Growth Factor Receptor 2 by the Extracellular Signal-Regulated Kinase Signaling Pathway in a Neonatal Rat Model of Periventricular White Matter Damage","volume":"38","author":"Yuan","year":"2016","journal-title":"Zhongguo Yi Xue Ke Xue Yuan Xue Bao"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00401-011-0930-z","article-title":"Less than Perfect Divorces: Dysregulated Mitochondrial Fission and Neurodegeneration","volume":"123","author":"Oettinghaus","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Serdar, M., Herz, J., Kempe, K., Winterhager, E., Jastrow, H., Heumann, R., Felderhoff-M\u00fcser, U., and Bendix, I. (2018). Protection of Oligodendrocytes Through Neuronal Overexpression of the Small GTPase Ras in Hyperoxia-Induced Neonatal Brain Injury. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00175"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1093\/hmg\/ddad130","article-title":"Macrocephaly and Developmental Delay Caused by Missense Variants in RAB5C","volume":"32","author":"Koop","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Barlow, H.R., and Cleaver, O. (2019). Building Blood Vessels\u2014One Rho GTPase at a Time. Cells, 8.","DOI":"10.3390\/cells8060545"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/21541248.2017.1364831","article-title":"Regulation of RhoA GTPase and Novel Target Proteins for ROCK","volume":"11","author":"Choi","year":"2020","journal-title":"Small GTPases"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/21541248.2017.1391365","article-title":"Fast-Cycling Rho GTPases","volume":"11","year":"2020","journal-title":"Small GTPases"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/humu.23964","article-title":"The Recurrent Postzygotic Pathogenic Variant p.Glu47Lys in RHOA Causes a Novel Recognizable Neuroectodermal Phenotype","volume":"41","author":"Yigit","year":"2020","journal-title":"Hum. 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