title: Rare ACTG1 variants in fetal microlissencephaly.
abstract: Heterozygous ACTG1 mutations are responsible for Baraitser-Winter cerebrofrontofacial syndrome which cortical malformation is characterized by pachygyria with frontal to occipital gradient of severity. We identified by whole exome sequencing in a cohort of 12 patients with prenatally diagnosed microlissencephaly, 2 foetal cases with missense mutations in the ACTG1 gene and in one case of living patient with typical Baraitser-Winter syndrome. Both foetuses and child exhibited microcephaly and facial dysmorphism consisting of microretrognatism, hypertelorism and low-set ears. Brain malformations included lissencephaly with an immature cortical plate, dysmorphic (2/3) or absent corpus callosum and vermian hypoplasia (2/3). Our results highlight the powerful diagnostic value of exome sequencing for patients with microlissencephaly, that may expand the malformation spectrum of ACTG1-related Baraitser-Winter cerebrofrontofacial syndrome and may suggest that ACTG1 could be added to the list of genes for assessing microlissencephaly.
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Poirier
authors.affiliation: Unit of Fetal Pathology, APHP, Antoine Beclere University Hospital, Clamart, France.
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic
authors.affiliation: Pathology Laboratory, Rouen University Hospital, France; NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, Institute of Research for Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Institut Imagine-INSERM UMR-1163, Embryology and Genetics of Congenital Malformations, Paris, France.
authors.forename: Mara
authors.initials: M
authors.lastname: Cavallin
authors.affiliation: Université de Montréal, CHU Sainte Justine, Montréal, QC, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallet-Bianco
authors.affiliation: Pediatric Neurology, Necker Enfants Malades University Hospital, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.affiliation: Pediatric Neurology, Trousseau University Hospital, Paris, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Valence
authors.affiliation: Pathology Laboratory, Centre hospitalier de Tulle, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Grande-Goburghun
authors.affiliation: Department of Clinical Genetics, Clermont Ferrand University Hospital, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.affiliation: Centre National de Génotypage, Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Centre National de Génotypage, Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Pôle de biologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Genetics and et Pathophysiology of Neurodeveloppemental and Epileptogenic Disorders, IGBMC, Illkirch, France.
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Institut Imagine-INSERM UMR-1163, Embryology and Genetics of Congenital Malformations, Paris, France. Electronic address: nadia.bahi-buisson@nck.aphp.fr.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000025:Abortion, Eugenic; D000199:Actins / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002648:Child; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D059472:Exome; D005091:Exons; D005260:Female; D005333:Fetus; D015870:Gene Expression; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007438:Introns; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense
chemical_list: C000594243:ACTG1 protein, human; D000199:Actins
keywords: Baraitser–Winter syndrome; Microlissencephaly