Functional analysis of a de novo ACTB mutation in a patient with atypical baraitser-winter syndrome

Jennifer J. Johnston, Kuo Kuang Wen, Kim Keppler-Noreuil, Melissa Mckane, Jessica L. Maiers, Alexander Greiner, Julie C. Sapp, Kris A. Demali, Peter A. Rubenstein, Leslie G. Biesecker

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Exome sequence analysis can be instrumental in identifying the genetic etiology behind atypical disease. We report a patient presenting with microcephaly, dysmorphic features, and intellectual disability with a tentative diagnosis of Dubowitz syndrome. Exome analysis was performed on the patient and both parents. A de novo missense variant was identified in ACTB, c.349G>A, p.E117K. Recent work in Baraitser-Winter syndrome has identified ACTB and ACTG1 mutations in a cohort of individuals, and we rediagnosed the patient with atypical Baraitser-Winter syndrome. We performed functional characterization of the variant actin and show that it alters cell adhesion and polymer formation supporting its role in disease. We present the clinical findings in the patient, comparison of this patient to other patients with ACTB/ACTG1 mutations, and results from actin functional studies that demonstrate novel functional attributes of this mutant protein.

Original languageEnglish (US)
Pages (from-to)1242-1249
Number of pages8
JournalHuman mutation
Issue number9
StatePublished - Sep 2013

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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