Source:Pediatric Neurology
Author(s): Gretchen Kissel Foskett, Edgar Engleman, Jenna Klotz, Okmi Choi, Lorna Tolentino, Aaina Kochhar, Qian Zhou Yang, David A. Stevenson
BackgroundBiallelic variants in PIGW have been suggested to cause infantile spasms and hyperphosphatasia. PIGW encodes for a protein involved in the third step of glycosylphosphatidylinositol (GPI) synthesis. GPI anchored proteins are increasingly recognized as important structures for cellular interactions and neuronal development.MethodsMolecular testing of PIGW was performed followed by fluorescence activating cell sorting (FACS) analysis of granulocytes, lymphocytes and monocytes and compared to controls.FindingsAn infant was homozygous for variants in PIGW (c.199C>G; p.Pro67Ala) with an associated phenotype of infantile spasms, myoclonic seizures, cortical visual impairment, developmental delay and minor dysmorphic features. Alkaline phosphatase levels ranged from normal to mildly elevated. Flow cytometric studies showed significantly decreased expression of important GPIs, providing functional evidence of pathogenicity.ConclusionOur data provide further evidence of a novel autosomal recessive PIGW-related epilepsy disorder. Flow cytometry provided functional evidence of the pathogenicity of homozygous variants of uncertain significance in PIGW, and supports the use of flow cytometry as a functional tool to demonstrate decreased surface expression of GPI anchored proteins in cases where there are variants of unknown significance.
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