Mutations in the glycosylphosphatidylinositol gene PIGL cause CHIME syndrome.

Ng, Bobby G; Hackmann, Karl; Jones, Melanie A; Eroshkin, Alexey M; He, Ping; Wiliams, Roy; Bhide, Shruti; Cantagrel, Vincent et al. · Am J Hum Genet · 2012

basic_science · Level V

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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.

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