title: Update on the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome.
abstract: Baraitser-Winter cerebrofrontofacial syndrome is caused by heterozygous missense mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1. Recently, we characterized the large cohort of 41 patients presenting with this condition. Our series contained 34 patients with mutations in ACTB and only nine with ACTG1 mutations. Here, we report on seven unrelated patients with six mutations in ACTG1-four novel and two previously reported. Only one of seven patients was clinically diagnosed with this disorder and underwent ACTB/ACTG1 targeted sequencing, four patients were screened as a part of the large lissencephaly cohort and two were tested with exome sequencing. Retrospectively, facial features were compatible with the diagnosis but significantly milder than previously reported in four patients, and non-specific in one. The pattern of malformations of cortical development was highly similar in four of six patients with available MRI images and encompassed frontal predominant pachygyria merging with the posterior predominant band heterotopia. Two remaining patients showed mild involvement consistent with bilaterally simplified gyration over the frontal lobes. Taken together, we expand the clinical spectrum of the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany. nataliya.didonato@uniklinikum-dresden.de.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Di Donato
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany.
authors.forename: Alma
authors.initials: A
authors.lastname: Kuechler
authors.affiliation: Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Vergano
authors.affiliation: Praxis für Humangenetik Cottbus, Cottbus, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Heinritz
authors.affiliation: Medical College of Virginia, Department of Human and Molecular Genetics, Richmond, Virginia.
authors.forename: Joann
authors.initials: J
authors.lastname: Bodurtha
authors.affiliation: Department of Pediatric Neurology, New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York.
authors.forename: Sabiha R
authors.initials: SR
authors.lastname: Merchant
authors.affiliation: Department of Pediatric Neurology, Gillette Children's Specialty Healthcare, St. Paul, Minnesota.
authors.forename: Galen
authors.initials: G
authors.lastname: Breningstall
authors.affiliation: Penn State Hershey Children's Hospital, Hershey, Pennsylvania.
authors.forename: Roger
authors.initials: R
authors.lastname: Ladda
authors.affiliation: Penn State Hershey Children's Hospital, Hershey, Pennsylvania.
authors.forename: Susan
authors.initials: S
authors.lastname: Sell
authors.affiliation: Cologne Center for Genomics, Cologne, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.affiliation: Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Bögershausen
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Timms
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Hackmann
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Evelin
authors.initials: E
authors.lastname: Schrock
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Sarah
authors.initials: S
authors.lastname: Collins
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Carissa
authors.initials: C
authors.lastname: Olds
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rump
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.|Department of Pediatrics, University of Washington, Seattle, Washington.|Department of Neurology, University of Washington, Seattle, Washington.
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000199:Actins / Q000235:genetics*; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: C000594243:ACTG1 protein, human; D000199:Actins; D015415:Biomarkers
keywords: ACTB; ACTG1; Baraister-Winter cerebro-fronto-facial syndrome; lissencephaly; malformation of cortical development