2. Academic Validation
  3. Microcephaly-dystonia due to mutated PLEKHG2 with impaired actin polymerization

Microcephaly-dystonia due to mutated PLEKHG2 with impaired actin polymerization

  • Neurogenetics. 2016 Jan;17(1):25-30. doi: 10.1007/s10048-015-0464-y.
Simon Edvardson 1 2,  Haibo Wang 3 4,  Talya Dor 2,  Osamah Atawneh 5,  Barak Yaacov 1,  Jutta Gartner 6,  Yuval Cinnamon 1,  Songhai Chen 7 8,  Orly Elpeleg 9
Affiliations

Affiliations

  • 1 Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 2 Pediatric Neurology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 3 Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • 4 Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • 5 Department of Pediatrics, Palestinian Red Cross Society Hospital, Hebron, Palestine.
  • 6 Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Göttingen, Germany.
  • 7 Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA. songhai-chen@uiowa.edu.
  • 8 Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA. songhai-chen@uiowa.edu.
  • 9 Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Elpeleg@hadassah.org.il.
PMID: 26573021 DOI: 10.1007/s10048-015-0464-y
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.

Keywords

Actin; Dystonia; Microcephaly; PLEKHG2.

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