title: RBPJ mutations identified in two families affected by Adams-Oliver syndrome.
abstract: Through exome resequencing, we identified two unique mutations in recombination signal binding protein for immunoglobulin kappa J (RBPJ) in two independent families affected by Adams-Oliver syndrome (AOS), a rare multiple-malformation disorder consisting primarily of aplasia cutis congenita of the vertex scalp and transverse terminal limb defects. These identified mutations link RBPJ, the primary transcriptional regulator for the Notch pathway, with AOS, a human genetic disorder. Functional assays confirmed impaired DNA binding of mutated RBPJ, placing it among other notch-pathway proteins altered in human genetic syndromes.
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, University of Oklahoma Children's Physicians Building, 1200 Children's Avenue, Oklahoma City, OK 73104, USA. susan-hassed@OUHSC.edu
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hassed
authors.forename: Graham B
authors.initials: GB
authors.lastname: Wiley
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Wang
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Shibo
authors.initials: S
authors.lastname: Li
authors.forename: Weihong
authors.initials: W
authors.lastname: Xu
authors.forename: Zhizhuang J
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: John J
authors.initials: JJ
authors.lastname: Mulvihill
authors.forename: James
authors.initials: J
authors.lastname: Robertson
authors.forename: James
authors.initials: J
authors.lastname: Warner
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics* / Q000378:metabolism; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012536:Scalp Dermatoses / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C497570:RBPJ protein, human; C078493:HES1 protein, human