Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.
Ana Marín-Quílez, Lorena Díaz-Ajenjo, Christian A Di Buduo, Ana Zamora-Cánovas, María Luisa Lozano, Rocío Benito, José Ramón González-Porras, Alessandra Balduini, José Rivera, José María Bastida
Author Information
Ana Marín-Quílez: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-U765, 30003 Murcia, Spain.
Lorena Díaz-Ajenjo: IBSAL, CIC, IBMCC, Universidad de Salamanca-CSIC, 37007 Salamanca, Spain.
Christian A Di Buduo: Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy. ORCID
Ana Zamora-Cánovas: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-U765, 30003 Murcia, Spain.
María Luisa Lozano: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-U765, 30003 Murcia, Spain. ORCID
Rocío Benito: IBSAL, CIC, IBMCC, Universidad de Salamanca-CSIC, 37007 Salamanca, Spain. ORCID
José Ramón González-Porras: Department of Hematology, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigación Biomédica de Salamanca (IBSAL), Universidad de Salamanca (USAL), 37007 Salamanca, Spain.
Alessandra Balduini: Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy.
José Rivera: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-U765, 30003 Murcia, Spain. ORCID
José María Bastida: Department of Hematology, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigación Biomédica de Salamanca (IBSAL), Universidad de Salamanca (USAL), 37007 Salamanca, Spain. ORCID
Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance. Platelets have a half-life in blood ranging from 8 to 11 days, after which they lose the final sialic acid and are recognized by receptors in the liver and eliminated from the bloodstream. This favors the transduction of thrombopoietin, which induces megakaryopoiesis to produce new platelets. More than two hundred enzymes are responsible for proper glycosylation and sialylation. In recent years, novel disorders of glycosylation caused by molecular variants in multiple genes have been described. The phenotype of the patients with genetic alterations in and is consistent with syndromic manifestations, severe inherited thrombocytopenia, and hemorrhagic complications.
