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. Epub 2012 Mar 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics*
  • Bacterial Toxins / biosynthesis
  • Base Sequence
  • CD59 Antigens / biosynthesis
  • Cells, Cultured
  • Coloboma / genetics*
  • Exome / genetics
  • Glycosylphosphatidylinositols / metabolism
  • Hearing Loss, Conductive / genetics*
  • Heart Defects, Congenital / genetics*
  • Humans
  • Ichthyosis / genetics*
  • Intellectual Disability / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Neurocutaneous Syndromes
  • Pore Forming Cytotoxic Proteins / biosynthesis

Substances

  • Bacterial Toxins
  • CD59 Antigens
  • Glycosylphosphatidylinositols
  • Pore Forming Cytotoxic Proteins
  • CD59 protein, human
  • aerolysin
  • Amidohydrolases
  • N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase

Supplementary concepts

  • Zunich neuroectodermal syndrome