{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:47:28Z","timestamp":1782150448931,"version":"3.54.5"},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The Rho GTPase gene family plays a crucial role in key cellular functions. RAC3, one of the three genes in this family, along with RAC1 and RAC2, is highly expressed in the brain. It is specifically involved in neuronal differentiation, maturation, and migration. Therefore, dysregulation of RAC3 can lead to neurodevelopmental abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we report two siblings, born to a nonconsanguineous couple, with global developmental delay, intellectual disability, and facial dysmorphism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Whole exome sequencing revealed a pathogenic heterozygous variant, c.184G&gt;A (p.Glu62Lys), in exon 3 of the RAC3 gene [NM_005052.3], which is associated with neurodevelopmental disorder (NDD) with structural brain anomalies and dysmorphic facies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RAC3-associated disorder should be considered as a differential diagnosis in children with NDDs and characteristic facial dysmorphism, including arched eyebrows, hypertelorism, and prominent eyes, along with central nervous system abnormalities. In our cases, we observed novel MRI brain findings that had not been previously reported, thereby expanding the spectrum of brain anomalies associated with this condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/mcd.0000000000000540","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T02:03:39Z","timestamp":1762481019000},"page":"1-6","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Recurrent RAC3 related neuro-rachopathy in a pair of Indian siblings with novel findings: expanding the spectrum of brain anomalies"],"prefix":"10.1097","volume":"35","author":[{"given":"Gayatri","family":"Nerakh","sequence":"first","affiliation":[{"name":"Department of Genetics, Fernandez Hospital, Hyderabad"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth Rao","family":"Dhareneni","sequence":"additional","affiliation":[{"name":"Department of Genetics, Fernandez Hospital, Hyderabad"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udhaya","family":"Kotecha","sequence":"additional","affiliation":[{"name":"Neuberg Center for Genomic Medicine, Ahmedabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"R1-20260622","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1046\/j.1460-9568.2003.02938.x","article-title":"Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiation.","volume":"18","author":"Bolis","year":"2003","journal-title":"Eur J Neurosci"},{"key":"R2-20260622","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/pd.6106","article-title":"Prenatal imaging features related to RAC3 pathogenic variant and differential diagnoses.","volume":"42","author":"Cabet","year":"2022","journal-title":"Prenat Diagn"},{"key":"R3-20260622","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1096\/fj.08-121574","article-title":"Essential role of Rac1 and Rac3 GTPases in neuronal development.","volume":"23","author":"Corbetta","year":"2009","journal-title":"FASEB J"},{"key":"R4-20260622","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s41436-018-0323-y","article-title":"De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome.","volume":"21","author":"Costain","year":"2019","journal-title":"Genet Med"},{"key":"R5-20260622","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s10038-019-0656-7","article-title":"A de novo variant in RAC3 causes severe global developmental delay and a middle interhemispheric variant of holoprosencephaly.","volume":"64","author":"Hiraide","year":"2019","journal-title":"J Hum Genet"},{"key":"R6-20260622","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1007\/s00381-024-06285-z","article-title":"An unusual presentation of de novo RAC3 variation in prenatal diagnosis.","volume":"40","author":"Meunier","year":"2024","journal-title":"Childs Nerv Syst"},{"key":"R7-20260622","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1136\/jmedgenet-2022-108483","article-title":"Gain-of-function p. F28S variant in RAC3 disrupts neuronal differentiation, migration and axonogenesis during cortical development, leading to neurodevelopmental disorder.","volume":"60","author":"Nishikawa","year":"2023","journal-title":"J Med Genet"},{"key":"R11-20260622","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":"R8-20260622","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.3390\/cells10123395","article-title":"Pathophysiological mechanisms in neurodevelopmental disorders caused by Rac GTPases dysregulation: what\u2019s behind neuro-RACopathies.","volume":"10","author":"Scala","year":"2021","journal-title":"Cells"},{"key":"R9-20260622","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1093\/brain\/awac106","article-title":"Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes.","volume":"145","author":"Scala","year":"2022","journal-title":"Brain"},{"key":"R10-20260622","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3389\/fncel.2014.00314","article-title":"Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration.","volume":"8","author":"Stankiewicz","year":"2014","journal-title":"Front Cell Neurosci"}],"container-title":["Clinical Dysmorphology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000540","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:00:17Z","timestamp":1782147617000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/mcd.0000000000000540","relation":{},"ISSN":["0962-8827","1473-5717"],"issn-type":[{"value":"0962-8827","type":"print"},{"value":"1473-5717","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]},"assertion":[{"value":"2025-04-18","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-15","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}