Case report: Functional characterization of a de novo c.145G>A p.Val49Met pathogenic variant in a case of PIGA-CDG with megacolon

Roberta Salinas-Marín; Yoshiko Murakami; Carlos Alberto González-Domínguez; Mario Ernesto Cruz-Muñoz; Héctor Manuel Mora-Montes; Eva Morava; Taroh Kinoshita; Susana Monroy-Santoyo; Iván Martínez-Duncker

doi:10.3389/fgene.2022.971473

Case report: Functional characterization of a de novo c.145G>A p.Val49Met pathogenic variant in a case of PIGA-CDG with megacolon

Front Genet. 2022 Oct 17:13:971473. doi: 10.3389/fgene.2022.971473. eCollection 2022.

Affiliations

¹ Laboratorio de Glicobiología Humana y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
² Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
³ Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
⁴ Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
⁵ Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato, México.
⁶ Department of Clinical Genomics, Mayo Clinic, Rochester, MN, United States.
⁷ Department of Medical Genetics, University of Pecs Medical School, Pecs, Hungary.
⁸ Frontiers in Congenital Disorders of Glycosylation Consortium, National Institute of Neurological Diseases and Stroke (NINDS), National Institute of Child Health and Human Development (NICHD) and the National Center for Advancing Translational Sciences (NCATS), and the Rare Disorders Clinical Research Network (RDCRN), Bethesda, MD, United States.
⁹ Centro de Investigación Traslacional, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, México.

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.

Keywords: CD59 antigen; CDG (congenital disorder of glycosylation); GPI (glycosylphosphatidylinositol); PIGA; exome.

Publication types

Case Reports