AUTHOR=Salinas-Marín Roberta , Murakami Yoshiko , González-Domínguez Carlos Alberto , Cruz-Muñoz Mario Ernesto , Mora-Montes Héctor Manuel , Morava Eva , Kinoshita Taroh , Monroy-Santoyo Susana , Martínez-Duncker Iván TITLE=Case report: Functional characterization of a de novo c.145G>A p.Val49Met pathogenic variant in a case of PIGA-CDG with megacolon JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.971473 DOI=10.3389/fgene.2022.971473 ISSN=1664-8021 ABSTRACT=

A subgroup of congenital disorders of glycosylation (CDGs) includes inherited GPI-anchor deficiencies (IGDs) that affect the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, including the first reaction catalyzed by the X-linked PIGA. Here, we show the first PIGA-CDG case reported in Mexico in a male child with a moderate-to-severe phenotype characterized by neurological and gastrointestinal symptoms, including megacolon. Exome sequencing identified the hemizygous variant PIGA c.145G>A (p.Val49Met), confirmed by Sanger sequencing and characterized as de novo. The pathogenicity of this variant was characterized by flow cytometry and complementation assays in PIGA knockout (KO) cells.