title: Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome.
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.
authors: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Jennifer J
authors: JJ
authors: Johnston
authors: Kuo-Kuang
authors: KK
authors: Wen
authors: Kim
authors: K
authors: Keppler-Noreuil
authors: Melissa
authors: M
authors: McKane
authors: Jessica L
authors: JL
authors: Maiers
authors: Alexander
authors: A
authors: Greiner
authors: Julie C
authors: JC
authors: Sapp
authors: Kris A
authors: KA
authors: Demali
authors: Peter A
authors: PA
authors: Rubenstein
authors: Leslie G
authors: LG
authors: Biesecker
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics; D059472:Exome; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008831:Microcephaly / Q000235:genetics; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: C526913:ACTC1 protein, human; D000199:Actins
keywords: ACTB; Baraitser-Winter syndrome; Dubowitz; actin
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