title: Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome.
abstract: Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family.
authors.affiliation: Center for Human Genetics, Catholic University Leuven, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Jeroen K J
authors.initials: JK
authors.lastname: Van Houdt
authors.forename: Beata Anna
authors.initials: BA
authors.lastname: Nowakowska
authors.forename: Sérgio B
authors.initials: SB
authors.lastname: Sousa
authors.forename: Barbera D C
authors.initials: BD
authors.lastname: van Schaik
authors.forename: Eve
authors.initials: E
authors.lastname: Seuntjens
authors.forename: Nelson
authors.initials: N
authors.lastname: Avonce
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sifrim
authors.forename: Omar A
authors.initials: OA
authors.lastname: Abdul-Rahman
authors.forename: Marie-José H
authors.initials: MJ
authors.lastname: van den Boogaard
authors.forename: Armand
authors.initials: A
authors.lastname: Bottani
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.forename: Isabel
authors.initials: I
authors.lastname: Filges
authors.forename: Alan
authors.initials: A
authors.lastname: Fryer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Simone
authors.initials: S
authors.lastname: Gana
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Hall
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
authors.forename: Jakub
authors.initials: J
authors.lastname: Klapecki
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Alma
authors.initials: A
authors.lastname: Kuechler
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Lines
authors.forename: Saskia
authors.initials: S
authors.lastname: Maas
authors.forename: Kay D
authors.initials: KD
authors.lastname: Macdermot
authors.forename: Shane
authors.initials: S
authors.lastname: McKee
authors.forename: Alex
authors.initials: A
authors.lastname: Magee
authors.forename: Stella A
authors.initials: SA
authors.lastname: de Man
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
authors.forename: Fanny
authors.initials: F
authors.lastname: Morice-Picard
authors.forename: Ewa
authors.initials: E
authors.lastname: Obersztyn
authors.forename: Jacek
authors.initials: J
authors.lastname: Pilch
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rosser
authors.forename: Nora
authors.initials: N
authors.lastname: Shannon
authors.forename: Irene
authors.initials: I
authors.lastname: Stolte-Dijkstra
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dijck
authors.forename: Catheline
authors.initials: C
authors.lastname: Vilain
authors.forename: Annick
authors.initials: A
authors.lastname: Vogels
authors.forename: Emma
authors.initials: E
authors.lastname: Wakeling
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Louise
authors.initials: L
authors.lastname: Wilson
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Antoine H C
authors.initials: AH
authors.lastname: van Kampen
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.forename: Raoul
authors.initials: R
authors.lastname: Hennekam
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D019066:Facies; D005532:Foot Deformities, Congenital / Q000235:genetics*; D005809:Genes, Regulator; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C084011:SMARCA2 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors