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=Volume 13 - 2022

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 (CDG) include inherited GPI-anchor deficiencies (IGD) that affect the biosynthesis of glycophosphatidylinositol (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.