Mutations in the Glycosylphosphatidylinositol Gene PIGL Cause CHIME Syndrome

• DOI: 10.1016/j.ajhg.2012.02.010
• Publication Date: 2012-03-22T18:04:17Z
• Authors: Bobby G. Ng; Karl Hackmann; Melanie A. Jones; Alexey M. Eroshkin; Ping He; Roy Wiliams; Shruti Bhide; Vincent Cantagrel; Joseph G. Gleeson; Amy S. Paller; Rhonda E. Schnur; Sigrid Tinschert; Janice Zunich; Madhuri R. Hegde; Hudson H. Freeze
• Keywords: Heart Defects, Congenital; Pore Forming Cytotoxic Proteins; 0301 basic medicine; Base Sequence; Glycosylphosphatidylinositols; Neurocutaneous Syndromes; Bacterial Toxins; Hearing Loss, Conductive; Molecular Sequence Data; Ichthyosis; CD59 Antigens; Amidohydrolases; Coloboma; 03 medical and health sciences; Intellectual Disability; Mutation; Genetics; Humans; Genetics(clinical); Exome; Cells, Cultured

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.