Contract grant sponsors: National Institutes of Health (#DC8803); National Science Foundation (#1120478).
Functional Analysis of a De Novo ACTB Mutation in a Patient with Atypical Baraitser–Winter Syndrome
Article first published online: 28 MAY 2013
© 2013 WILEY PERIODICALS, INC.
Volume 34, Issue 9, pages 1242–1249, September 2013
How to Cite
Johnston, J. J., Wen, K.-K., Keppler-Noreuil, K., McKane, M., Maiers, J. L., Greiner, A., Sapp, J. C., NIH Intramural Sequencing Center, DeMali, K. A., Rubenstein, P. A. and Biesecker, L. G. (2013), Functional Analysis of a De Novo ACTB Mutation in a Patient with Atypical Baraitser–Winter Syndrome. Hum. Mutat., 34: 1242–1249. doi: 10.1002/humu.22350
Communicated by Richard A. Gibbs
These authors contributed equally to this work.
- Issue published online: 14 AUG 2013
- Article first published online: 28 MAY 2013
- Accepted manuscript online: 6 MAY 2013 09:18AM EST
- Manuscript Accepted: 30 APR 2013
- Manuscript Received: 4 FEB 2013
- National Institutes of Health. Grant Number: #DC8803
- National Science Foundation. Grant Number: #1120478
- Baraitser–Winter syndrome
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.