hes1-protein--human and Scalp-Dermatoses

Adams-Oliver syndrome (AOS) is a rare hereditary disorder characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects. The etiology of AOS has remained largely unknown, although mutations in the notch receptor 1 (

Topics: Amino Acid Sequence; Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Child; China; Ectodermal Dysplasia; Frameshift Mutation; Humans; Limb Deformities, Congenital; Male; Models, Molecular; Protein Conformation; Receptor, Notch1; Repressor Proteins; Scalp Dermatoses; Transcription Factor HES-1

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.

Topics: Basic Helix-Loop-Helix Transcription Factors; Chromatin Immunoprecipitation; Ectodermal Dysplasia; Electrophoretic Mobility Shift Assay; Female; Genetic Predisposition to Disease; HEK293 Cells; Homeodomain Proteins; Humans; Immunoglobulin J Recombination Signal Sequence-Binding Protein; Limb Deformities, Congenital; Male; Mutation; Pedigree; Polymerase Chain Reaction; Promoter Regions, Genetic; Protein Structure, Tertiary; Receptors, Notch; Scalp Dermatoses; Transcription Factor HES-1