Novel GNE Gene Variants Associated with Severe Congenital Thrombocytopenia and Platelet Sialylation Defect. Thromb Haemost 2022 Jul;122(7):1139-1146
Date
01/21/2022Pubmed ID
35052006Pubmed Central ID
PMC10064489DOI
10.1055/s-0041-1742207Scopus ID
2-s2.0-85130195438 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
The GNE gene encodes an enzyme that initiates and regulates the biosynthesis of N-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 novel compound heterozygous variants in GNE 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 N-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.
Author List
Zieger B, Boeckelmann D, Anani W, Falet H, Zhu J, Glonnegger H, Full H, Andresen F, Erlacher M, Lausch E, Fels S, Strahm B, Lang P, Hoffmeister KMAuthor
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blood PlateletsDistal Myopathies
Female
Humans
Multienzyme Complexes
Mutation
N-Acetylneuraminic Acid
Thrombocytopenia
