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

被引：19

作者：

Zieger, Barbara ^{[1
]}

Boeckelmann, Doris ^{[1
]}

Anani, Waseem ^{[2
]}

Falet, Herve ^{[2
,3
]}

Zhu, Jieqing ^{[2
,4
]}

Glonnegger, Hannah ^{[1
]}

Full, Hermann ^{[5
]}

Andresen, Felicia ^{[1
]}

Erlacher, Miriam ^{[1
]}

Lausch, Ekkehart ^{[6
]}

Fels, Salome ^{[1
]}

Strahm, Brigitte ^{[1
]}

Lang, Peter ^{[7
]}

Hoffmeister, Karin M. ^{[2
,8
]}

机构：

[1] Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Med Ctr,Fac Med, D-79085 Freiburg, Germany

[2] Versiti Blood Res Inst, Translat Glyc Ctr, Milwaukee, WI USA

[3] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA

[4] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA

[5] SLK Kliniken Heilbronn, Clin Pediat & Adolescent Med, Heilbronn, Germany

[6] Univ Freiburg, Dept Pediat, Pediat Genet Sect, Freiburg, Germany

[7] Univ Tubingen, Childrens Univ Hosp, Dept Pediat, Tubingen, Germany

[8] Med Coll Wisconsin, Dept Biochem & Med, Milwaukee, WI 53226 USA

来源：

THROMBOSIS AND HAEMOSTASIS | 2022年 / 122卷 / 07期

基金：

美国国家卫生研究院;

关键词：

platelet disorders; congenital thrombocytopenia; GNE; lectin; SIALIC-ACID; KINASE; CLEARANCE;

D O I：

10.1055/s-0041-1742207

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 alpha-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.

引用

页码：1139 / 1146

页数：8

共 26 条

[1]

[Anonymous], 2019, R PACKAGE VERS

[2] Mutation Update for GNE Gene Variants Associated with GNE Myopathy [J].