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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.

SUBMITTER: Ng BG

PROVIDER: S-EPMC3322218 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Mutations in the glycosylphosphatidylinositol gene PIGL cause CHIME syndrome.

Ng Bobby G BG Hackmann Karl K Jones Melanie A MA Eroshkin Alexey M AM He Ping P Wiliams Roy R Bhide Shruti S Cantagrel Vincent V Gleeson Joseph G JG Paller Amy S AS Schnur Rhonda E RE Tinschert Sigrid S Zunich Janice J Hegde Madhuri R MR Freeze Hudson H HH

American journal of human genetics 20120322 4

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-bin ...[more]

PMID: 22444671

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Large deletion in PIGL: a common mutational mechanism in CHIME syndrome?

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Child with a mild CHIME syndrome phenotype and carrying a novel p.(Asp52Asn) PIGL pathogenic variant in association with the previously reported p.(Leu167Pro) variant: A case report.

Project description:Coloboma, congenital heart disease, ichthyosiform dermatosis, mental retardation, and ear anomalies (CHIME) syndrome is a very rare autosomal recessive neuroectodermal disorder related to PIGL gene mutations. Here, we report a patient who showed an initial delay in psychomotor development and skin abnormalities consistent with CHIME syndrome but with atypical clinical features and laboratory findings. In line with our clinical suspicion, the c.500T>C, p.(Leu167Pro) variant (found in all the previously described cases of CHIME syndrome) was found on the paternal allele. A novel "likely pathogenic" PIGL missense variant (c.154G>A, p.(Asp52Asn)) was detected on the maternal allele. This case provides new insights into the clinical spectrum of CHIME syndrome and highlights the potential for phenotypic/genotypic variations.

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INTS8 mutations cause severe neurodevelopmental syndrome

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