Novel GNE Gene Variants Associated with Severe Congenital Thrombocytopenia and Platelet Sialylation Defect

• Published in: Thrombosis and haemostasis Vol. 122; no. 7; p. 1139
• Main Authors: Zieger, Barbara, Boeckelmann, Doris, Anani, Waseem, Falet, Hervé, Zhu, Jieqing, Glonnegger, Hannah, Full, Hermann, Andresen, Felicia, Erlacher, Miriam, Lausch, Ekkehart, Fels, Salome, Strahm, Brigitte, Lang, Peter, Hoffmeister, Karin M
• Format: Journal Article
• Language: English
• Published: Germany 01.07.2022
• Subjects: Blood Platelets; Distal Myopathies - genetics; Female; Humans; Multienzyme Complexes - chemistry; Multienzyme Complexes - genetics; Mutation; N-Acetylneuraminic Acid; Thrombocytopenia - genetics
• DOI: 10.1055/s-0041-1742207

The gene encodes an enzyme that initiates and regulates the biosynthesis of -acetylneuraminic acid, a precursor of sialic acids. GNE mutations are classically associated with Nonaka myopathy and sialuria, following an autosomal recessive and autosomal dominant inheritance pattern. Reports show that single GNE variants cause severe thrombocytopenia without muscle weakness. Using panel sequencing, we identified two compound heterozygous variants in in a young girl with life-threatening bleedings, severe congenital thrombocytopenia, and a platelet secretion defect. Both variants are located in the nucleotide-binding site of the -acetylmannosamin kinase domain of GNE. Lectin array showed decreased α-2,3-sialylation on platelets, consistent with loss of sialic acid synthesis and indicative of rapid platelet clearance. Hematopoietic stem cell transplantation (HSCT) normalized platelet counts. This is the first report of an HSCT in a patient with an inherited GNE defect leading to normal platelet counts.