title: Mutations in the glycosylphosphatidylinositol gene PIGL cause CHIME syndrome.
abstract: CHIME syndrome is characterized by colobomas, heart defects, ichthyosiform dermatosis, mental retardation (intellectual disability), and ear anomalies, including conductive hearing loss. Whole-exome sequencing on five previously reported cases identified PIGL, the de-N-acetylase required for glycosylphosphatidylinositol (GPI) anchor formation, as a strong candidate. Furthermore, cell lines derived from these cases had significantly reduced levels of the two GPI anchor markers, CD59 and a GPI-binding toxin, aerolysin (FLAER), confirming the pathogenicity of the mutations.
authors.affiliation: Genetic Disease Program, Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Bobby G
authors.initials: BG
authors.lastname: Ng
authors.forename: Karl
authors.initials: K
authors.lastname: Hackmann
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Jones
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Eroshkin
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Roy
authors.initials: R
authors.lastname: Wiliams
authors.forename: Shruti
authors.initials: S
authors.lastname: Bhide
authors.forename: Vincent
authors.initials: V
authors.lastname: Cantagrel
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.forename: Rhonda E
authors.initials: RE
authors.lastname: Schnur
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
authors.forename: Janice
authors.initials: J
authors.lastname: Zunich
authors.forename: Madhuri R
authors.initials: MR
authors.lastname: Hegde
authors.forename: Hudson H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D001427:Bacterial Toxins / Q000096:biosynthesis; D001483:Base Sequence; D018957:CD59 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003103:Coloboma / Q000235:genetics*; D059472:Exome / Q000235:genetics; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006314:Hearing Loss, Conductive / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020752:Neurocutaneous Syndromes; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis
chemical_list: D001427:Bacterial Toxins; D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D052899:Pore Forming Cytotoxic Proteins; C051590:CD59 protein, human; C032676:aerolysin; D000581:Amidohydrolases; C087696:N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase