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

doi:10.1002/humu.22350

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Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome

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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 and Leslie G Biesecker

Human mutation, Vol.34(9), pp.1242-1249

09/2013

DOI: 10.1002/humu.22350

PMCID: PMC3745514

PMID: 23649928

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Abstract

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.

Dubowitz

actin

Baraitser-Winter syndrome

ACTB

Details

Title: Subtitle: Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome
Creators: Jennifer J Johnston - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Kuo-Kuang Wen - University of Iowa, Iowa City, IA, USA
Kim Keppler-Noreuil - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Melissa McKane - University of Iowa, Iowa City, IA, USA
Jessica L Maiers - University of Iowa, Iowa City, IA, USA
Alexander Greiner - University of Iowa, Iowa City, IA, USA
Julie C Sapp - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Kris A DeMali - University of Iowa, Iowa City, IA, USA
Peter A Rubenstein - University of Iowa, Iowa City, IA, USA
Leslie G Biesecker - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Resource Type: Journal article
Publication Details: Human mutation, Vol.34(9), pp.1242-1249
DOI: 10.1002/humu.22350
PMID: 23649928
PMCID: PMC3745514
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Grant note: Z99 HG999999 || HG / National Human Genome Research Institute : NHGRI R55 DC008803 || DC / National Institute on Deafness and Other Communication Disorders : NIDCD
Language: English
Date published: 09/2013
Academic Unit: Dermatology; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984024509402771

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