Mutations in the glycosylphosphatidylinositol gene PIGL cause CHIME syndrome

  • Am J Hum Genet. 2012 Apr 6;90(4):685-8. doi: 10.1016/j.ajhg.2012.02.010.
Bobby G Ng  1 ,  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
Affiliations
  • 1. Genetic Disease Program, Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
PMID: 22444671 DOI: 10.1016/j.ajhg.2012.02.010
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.