title: Microcephaly-dystonia due to mutated PLEKHG2 with impaired actin polymerization.
abstract: Rearrangement of the actin cytoskeleton is controlled by RhoGTPases which are activated by RhoGEFs. We identified homozygosity for Arg204Trp mutation in the Rho guanidine exchange factor (RhoGEF) PLEKHG2 gene in five patients with profound mental retardation, dystonia, postnatal microcephaly, and distinct neuroimaging pattern. The activity of the mutant PLEKHG2 was significantly decreased, both in basal state and when Gβγ- or lysophosphatidic acid (LPA)-stimulated. SDF1a-stimulated actin polymerization was significantly impaired in patient cells, and this abnormality was duplicated in control cells when PLEKHG2 expression was downregulated. These results underscore the role of PLEKHG2 in actin polymerization and delineate the clinical and radiological findings in PLEKHG2 deficiency.
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.|Pediatric Neurology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.|Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Pediatric Neurology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Talya
authors.initials: T
authors.lastname: Dor
authors.affiliation: Department of Pediatrics, Palestinian Red Cross Society Hospital, Hebron, Palestine.
authors.forename: Osamah
authors.initials: O
authors.lastname: Atawneh
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Yaacov
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Göttingen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Gartner
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Cinnamon
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA. songhai-chen@uiowa.edu.|Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA. songhai-chen@uiowa.edu.
authors.forename: Songhai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Elpeleg@hadassah.org.il.
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D000199:Actins / Q000378:metabolism*; D018912:Arabs; D003241:Consanguinity; D004421:Dystonia / Q000150:complications / Q000235:genetics*; D005190:Family; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000235:genetics*; D008877:Middle East; D020125:Mutation, Missense; D010375:Pedigree; D055503:Protein Multimerization / Q000235:genetics
chemical_list: D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; C527535:PLEKHG2 protein, human
keywords: Actin; Dystonia; Microcephaly; PLEKHG2