Inherited glycosylphosphatidylinositol defects cause the rare Emm-negative blood phenotype and developmental disorders Article Swipe

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Romain Duval , Gaël Nicolas , Alexandra Willemetz , Yoshiko Murakami , Mahmoud Mikdar , Cédric Vrignaud , Hisham Megahed , Jean‐Pierre Cartron , Cécile Masson , Samer Wehbi , Bérengère Koehl , Marie Hully , Karine Siquier-Pernet , Nicole Chemlay , Agnès Rötig , Stanislas Lyonnet , Yves Colin , Giulia Barcia , Vincent Cantagrel , Caroline Le Van Kim , Olivier Hermine , Taroh Kinoshita , Thierry Peyrard , Slim Azouzi ·

YOU? · · 2021 · Open Access · · DOI: https://doi.org/10.1182/blood.2020009810

Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 proteins to the cell surface. Pathogenic variants in several genes that participate in GPI biosynthesis cause inherited GPI deficiency disorders. Here, we reported that homozygous null alleles of PIGG, a gene involved in GPI modification, are responsible for the rare Emm-negative blood phenotype. Using a panel of K562 cells defective in both the GPI-transamidase and GPI remodeling pathways, we show that the Emm antigen, whose molecular basis has remained unknown for decades, is carried only by free GPI and that its epitope is composed of the second and third ethanolamine of the GPI backbone. Importantly, we show that the decrease in Emm expression in several inherited GPI deficiency patients is indicative of GPI defects. Overall, our findings establish Emm as a novel blood group system, and they have important implications for understanding the biological function of human free GPI.

Related Topics

Phenotype

Biology

Immunology

Concepts

Phenotype Epitope Glycolipid Allele Biology Gene Immunology Antigen Null allele Genetics

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Type: article
Language: en
Landing Page: https://doi.org/10.1182/blood.2020009810
PDF: https://ashpublications.org/blood/article-pdf/137/26/3660/1813153/bloodbld2020009810.pdf
OA Status: bronze
Cited By: 27
References: 33
Related Works: 10
OpenAlex ID: https://openalex.org/W3137865816

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OpenAlex ID: https://openalex.org/W3137865816

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DOI: https://doi.org/10.1182/blood.2020009810

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Title: Inherited glycosylphosphatidylinositol defects cause the rare Emm-negative blood phenotype and developmental disorders

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Type: article

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Language: en

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Publication year: 2021

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Publication date: 2021-03-24

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Authors: Romain Duval, Gaël Nicolas, Alexandra Willemetz, Yoshiko Murakami, Mahmoud Mikdar, Cédric Vrignaud, Hisham Megahed, Jean‐Pierre Cartron, Cécile Masson, Samer Wehbi, Bérengère Koehl, Marie Hully, Karine Siquier-Pernet, Nicole Chemlay, Agnès Rötig, Stanislas Lyonnet, Yves Colin, Giulia Barcia, Vincent Cantagrel, Caroline Le Van Kim, Olivier Hermine, Taroh Kinoshita, Thierry Peyrard, Slim Azouzi

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Landing page: https://doi.org/10.1182/blood.2020009810

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PDF URL: https://ashpublications.org/blood/article-pdf/137/26/3660/1813153/bloodbld2020009810.pdf

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OA status: bronze

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OA URL: https://ashpublications.org/blood/article-pdf/137/26/3660/1813153/bloodbld2020009810.pdf

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Concepts: Phenotype, Epitope, Glycolipid, Allele, Biology, Gene, Immunology, Antigen, Null allele, Genetics

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Cited by: 27

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Citations by year (recent): 2025: 3, 2024: 6, 2023: 5, 2022: 6, 2021: 6

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References (count): 33

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