{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:35:44Z","timestamp":1792056944111,"version":"4.4.0"},"reference-count":67,"publisher":"American Society of Hematology","issue":"4","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3\u00a0patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed 4 variants that affect GALE, 3 of those previously unreported (Pedigree A, p.Lys78ValfsX32 and p.Thr150Met; Pedigree B, p.Val128Met; and p.Leu223Pro). Platelet phenotype analysis showed giant and\/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease in N-acetyl-lactosamine (LacNAc), showing a hypoglycosylation pattern, reduced surface expression of gylcoprotein Ib\u03b1-IX-V (GPIb\u03b1-IX-V) complex and mature \u03b21 integrin, and increased apoptosis. In\u00a0vitro studies performed with patients-derived megakaryocytes showed normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylation of the GPIb\u03b1 and \u03b21 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand factor were also shown. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasizes the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function.<\/jats:p>","DOI":"10.1182\/blood.2022016995","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T19:15:54Z","timestamp":1668712554000},"page":"406-421","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":32,"title":["Novel variants in <i>GALE<\/i> cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-1919","authenticated-orcid":false,"given":"Ana","family":"Mar\u00edn-Qu\u00edlez","sequence":"first","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-2008","authenticated-orcid":false,"given":"Christian Andrea","family":"Di Buduo","sequence":"additional","affiliation":[{"name":"2Department of Molecular Medicine, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-385X","authenticated-orcid":false,"given":"Lorena","family":"D\u00edaz-Ajenjo","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8066-9895","authenticated-orcid":false,"given":"Vittorio","family":"Abbonante","sequence":"additional","affiliation":[{"name":"2Department of Molecular Medicine, University of Pavia, Pavia, Italy"},{"name":"3Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vuelta","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo Maria","family":"Soprano","sequence":"additional","affiliation":[{"name":"2Department of Molecular Medicine, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-7993","authenticated-orcid":false,"given":"Cristina","family":"Miguel-Garc\u00eda","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0729-207X","authenticated-orcid":false,"given":"Sandra","family":"Santos-M\u00ednguez","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-4597","authenticated-orcid":false,"given":"Inmaculada","family":"Serramito-G\u00f3mez","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1785-4988","authenticated-orcid":false,"given":"Pedro","family":"Ruiz-Sala","sequence":"additional","affiliation":[{"name":"4Centro de Diagn\u00f3stico de Enfermedades Moleculares, Universidad Aut\u00f3noma de Madrid, CIBERER, IdIPAZ, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jes\u00fas","family":"Pe\u00f1arrubia","sequence":"additional","affiliation":[{"name":"5Servicio de Hematolog\u00eda, Hospital Cl\u00ednico Universitario de Valladolid, Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Pardal","sequence":"additional","affiliation":[{"name":"6Servicio de Hematolog\u00eda, Hospital Virgen del Puerto, Plasencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9661-9371","authenticated-orcid":false,"given":"Jes\u00fas Mar\u00eda","family":"Hern\u00e1ndez-Rivas","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"},{"name":"7Servicio de Hematolog\u00eda, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca (USAL), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Gonz\u00e1lez-Porras","sequence":"additional","affiliation":[{"name":"7Servicio de Hematolog\u00eda, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca (USAL), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-2151","authenticated-orcid":false,"given":"Ignacio","family":"Garc\u00eda-Tu\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"},{"name":"8Departamento de Biomedicina y Biotecnolog\u00eda, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Benito","sequence":"additional","affiliation":[{"name":"1Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC), Universidad de Salamanca-Centro Superior de Investigaciones Cient\u00edficas (CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4225-6840","authenticated-orcid":false,"given":"Jos\u00e9","family":"Rivera","sequence":"additional","affiliation":[{"name":"9Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB)-Pascual Parrilla, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3145-1245","authenticated-orcid":false,"given":"Alessandra","family":"Balduini","sequence":"additional","affiliation":[{"name":"2Department of Molecular Medicine, University of Pavia, Pavia, Italy"},{"name":"10Department of Biomedical Engineering, Tufts University, Medford, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8007-3909","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Bastida","sequence":"additional","affiliation":[{"name":"7Servicio de Hematolog\u00eda, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca (USAL), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"1","key":"2023082817051143400_bib1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/09537104.2016.1171835","article-title":"Inherited thrombocytopenias\u2014recent advances in clinical and molecular aspects","volume":"28","author":"Balduini","year":"2017","journal-title":"Platelets"},{"key":"2023082817051143400_bib2","doi-asserted-by":"crossref","first-page":"100784","DOI":"10.1016\/j.blre.2020.100784","article-title":"Inherited thrombocytopenias: an updated guide for clinicians","volume":"48","author":"Pecci","year":"2021","journal-title":"Blood Rev"},{"issue":"9","key":"2023082817051143400_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms22094521","article-title":"Inherited platelet disorders: An updated overview","volume":"22","author":"Palma-Barqueros","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"9","key":"2023082817051143400_bib4","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1111\/jth.13777","article-title":"Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia","volume":"15","author":"Bastida","year":"2017","journal-title":"J\u00a0Thromb Haemost"},{"issue":"3","key":"2023082817051143400_bib5","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3390\/jcm10030533","article-title":"Learning the ropes of platelet count regulation: inherited thrombocytopenias","volume":"10","author":"Bury","year":"2021","journal-title":"J Clin Med"},{"issue":"1","key":"2023082817051143400_bib6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/bjh.17409","article-title":"Advances in understanding the pathogenesis of hereditary macrothrombocytopenia","volume":"195","author":"Collins","year":"2021","journal-title":"Br J Haematol"},{"issue":"5","key":"2023082817051143400_bib7","first-page":"666","article-title":"Megakaryocyte cytoskeletal proteins in platelet biogenesis and diseases","volume":"122","author":"Mbiandjeu","year":"2021","journal-title":"Thromb Haemost"},{"issue":"8","key":"2023082817051143400_bib8","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.3324\/haematol.2019.233197","article-title":"Inherited thrombocytopenias: history, advances and perspectives","volume":"105","author":"Nurden","year":"2020","journal-title":"Haematologica"},{"issue":"5","key":"2023082817051143400_bib9","first-page":"e12532","article-title":"Hemostatic phenotypes and genetic disorders","volume":"5","author":"Freson","year":"2021","journal-title":"Res Pr Thromb Haemost"},{"issue":"9","key":"2023082817051143400_bib10","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.3390\/ijms22094330","article-title":"Role of thrombopoietin receptor agonists in inherited thrombocytopenia","volume":"22","author":"Bastida","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"7","key":"2023082817051143400_bib11","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1111\/jth.14874","article-title":"Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells","volume":"18","author":"Lee-Sundlov","year":"2020","journal-title":"J\u00a0Thromb Haemost"},{"issue":"16","key":"2023082817051143400_bib12","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1182\/blood-2015-01-569129","article-title":"Regulating billions of blood platelets: Glycans and beyond","volume":"126","author":"Grozovsky","year":"2015","journal-title":"Blood"},{"issue":"3","key":"2023082817051143400_bib13","first-page":"759","article-title":"Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver","volume":"106","author":"Ma","year":"2021","journal-title":"Haematologica"},{"issue":"1","key":"2023082817051143400_bib14","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41467-019-14178-y","article-title":"\u03b24GALT1 controls \u03b21 integrin function to govern thrombopoiesis and hematopoietic stem cell homeostasis","volume":"11","author":"Giannini","year":"2020","journal-title":"Nat Commun"},{"issue":"17","key":"2023082817051143400_bib15","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1182\/blood-2018-04-845545","article-title":"GNE variants causing autosomal recessive macrothrombocytopenia without associated muscle wasting","volume":"132","author":"Revel-Vilk","year":"2018","journal-title":"Blood"},{"issue":"17","key":"2023082817051143400_bib16","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1182\/blood-2018-04-847798","article-title":"Mutation in GNE is associated with severe congenital thrombocytopenia","volume":"132","author":"Futterer","year":"2018","journal-title":"Blood"},{"issue":"4","key":"2023082817051143400_bib17","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1016\/j.ajpath.2011.06.012","article-title":"A\u00a0novel type of macrothrombocytopenia associated with a defect in \u03b12,3-sialylation","volume":"179","author":"Jones","year":"2011","journal-title":"Am J Pathol"},{"issue":"12","key":"2023082817051143400_bib18","doi-asserted-by":"crossref","first-page":"e613","DOI":"10.3324\/haematol.2018.198028","article-title":"A\u00a0mutation in the gene coding for the sialic acid transporter SLC35A1 is required for platelet life span but not proplatelet formation","volume":"103","author":"Kauskot","year":"2018","journal-title":"Haematologica"},{"issue":"1","key":"2023082817051143400_bib19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/hmg\/ddy334","article-title":"Inherited thrombocytopenia associated with mutation of UDP-galactose-4-epimerase (GALE)","volume":"28","author":"Seo","year":"2019","journal-title":"Hum Mol Genet"},{"issue":"5-6","key":"2023082817051143400_bib20","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000511343","article-title":"A\u00a0Case of udp-galactose 4\u2032-epimerase deficiency associated with dyshematopoiesis and atrioventricular valve malformations: An exceptional clinical phenotype explained by altered n-glycosylation with relative preservation of the leloir pathway","volume":"11","author":"Febres-Aldana","year":"2020","journal-title":"Mol. Syndromol"},{"issue":"10","key":"2023082817051143400_bib21","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1002\/ajmg.a.62384","article-title":"Expansion of the clinical phenotype of GALE deficiency","volume":"185","author":"Markovitz","year":"2021","journal-title":"Am J Med Genet Part A"},{"issue":"5","key":"2023082817051143400_bib22","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/jth.15672","article-title":"A\u00a0novel nonsense variant in TPM4 caused dominant macrothrombocytopenia, mild bleeding tendency and disrupted cytoskeleton remodeling","volume":"20","author":"Mar\u00edn-Qu\u00edlez","year":"2022","journal-title":"J\u00a0Thromb Haemost"},{"issue":"24","key":"2023082817051143400_bib23","doi-asserted-by":"crossref","first-page":"5453","DOI":"10.1182\/bloodadvances.2020004057","article-title":"Expanding the genetic spectrum of TUBB1- related thrombocytopenia","volume":"5","author":"Palma-Barqueros","year":"2021","journal-title":"Blood Adv"},{"issue":"5","key":"2023082817051143400_bib24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the american college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"2","key":"2023082817051143400_bib25","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10545-011-9291-y","article-title":"Newborn screening for galactosemia by a second-tier multiplex enzyme assay using UPLC-MS\/MS in dried blood spots","volume":"34","author":"Ko","year":"2011","journal-title":"J\u00a0Inherit Metab Dis"},{"key":"2023082817051143400_bib26","doi-asserted-by":"crossref","first-page":"e587751","DOI":"10.7554\/eLife.58775","article-title":"Miniaturized 3d bone marrow tissue model to assess response to thrombopoietin-receptor agonists in patients","volume":"10","author":"Di Buduo","year":"2021","journal-title":"Elife"},{"key":"2023082817051143400_bib27","doi-asserted-by":"crossref","first-page":"23213","DOI":"10.1038\/srep23213","article-title":"Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients","volume":"6","author":"Di Buduo","year":"2016","journal-title":"Sci Rep"},{"issue":"11","key":"2023082817051143400_bib28","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1111\/j.1538-7836.2008.03132.x","article-title":"Adhesive receptors, extracellular proteins and myosin IIA orchestrate proplatelet formation by human megakaryocytes","volume":"6","author":"Balduini","year":"2008","journal-title":"J\u00a0Thromb Haemost"},{"issue":"7","key":"2023082817051143400_bib29","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1111\/j.1742-4658.2009.06922.x","article-title":"Functional analysis of mutations in UDP-galactose-4-epimerase (GALE) associated with galactosemia in Korean patients using mammalian GALE-null cells","volume":"276","author":"Bang","year":"2009","journal-title":"FEBS J"},{"issue":"23","key":"2023082817051143400_bib30","doi-asserted-by":"crossref","first-page":"6170","DOI":"10.1111\/j.1742-4658.2005.05017.x","article-title":"Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase","volume":"272","author":"Timson","year":"2005","journal-title":"FEBS J"},{"issue":"5","key":"2023082817051143400_bib31","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/S0021-9258(17)49882-6","article-title":"Human UDP-galactose 4\u2032-epimerase (GALE) is required for cell-surface glycome structure and function","volume":"295","author":"Broussard","year":"2020","journal-title":"J\u00a0Biol Chem"},{"issue":"4","key":"2023082817051143400_bib32","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1055\/s-0040-1719028","article-title":"A\u00a0gold standard protocol for human megakaryocyte culture based on the analysis of 1,500 umbilical cord blood samples","volume":"121","author":"Di Buduo","year":"2021","journal-title":"Thromb Haemost"},{"issue":"16","key":"2023082817051143400_bib33","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1182\/blood.2019000014","article-title":"Key actor in platelet biology","volume":"134","author":"Rosa","year":"2019","journal-title":"Blood"},{"issue":"1","key":"2023082817051143400_bib34","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3324\/haematol.2017.171132","article-title":"Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders","volume":"103","author":"Bastida","year":"2018","journal-title":"Haematologica"},{"issue":"7","key":"2023082817051143400_bib35","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1055\/s-0039-1687889","article-title":"Molecular diagnosis of inherited coagulation and bleeding disorders","volume":"45","author":"Bastida","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"8","key":"2023082817051143400_bib36","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1111\/jth.14945","article-title":"Strengths and limitations of high-throughput sequencing for the diagnosis of inherited bleeding and platelet disorders","volume":"18","author":"Ver Donck","year":"2020","journal-title":"J\u00a0Thromb Haemost"},{"issue":"2","key":"2023082817051143400_bib37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s12013-020-00960-z","article-title":"Molecular dynamics, residue network analysis, and cross-correlation matrix to characterize the deleterious missense mutations in GALE causing galactosemia III","volume":"79","author":"Kumar","year":"2021","journal-title":"Cell Biochem Biophys"},{"issue":"1","key":"2023082817051143400_bib38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ymgme.2004.09.003","article-title":"Functional characterization of the K257R and G319E-hGALE alleles found in patients with ostensibly peripheral epimerase deficiency galactosemia","volume":"84","author":"Wasilenko","year":"2005","journal-title":"Mol Genet Metab"},{"issue":"2","key":"2023082817051143400_bib39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.gene.2013.04.061","article-title":"In silico prediction of the effects of mutations in the human UDP-galactose 4\u2019-epimerase gene: Towards a predictive framework for type III galactosemia","volume":"524","author":"McCorvie","year":"2013","journal-title":"Gene"},{"issue":"1","key":"2023082817051143400_bib40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1086\/498985","article-title":"Epimerase-deficiency galactosemia is not a binary condition","volume":"78","author":"Openo","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"2","key":"2023082817051143400_bib41","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1086\/302263","article-title":"Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia","volume":"64","author":"Wohlers","year":"1999","journal-title":"Am J Hum Genet"},{"issue":"6","key":"2023082817051143400_bib42","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1161\/01.RES.0000260913.95642.3b","article-title":"Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition","volume":"100","author":"Fischer","year":"2007","journal-title":"Circ Res"},{"issue":"12","key":"2023082817051143400_bib43","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1002\/dvdy.22458","article-title":"Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1","volume":"239","author":"Frieden","year":"2010","journal-title":"Dev Dyn"},{"issue":"15","key":"2023082817051143400_bib44","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1182\/blood.2020007265","article-title":"Increased B4GALT1 expression is associated with platelet surface galactosylation and thrombopoietin plasma levels in MPNs","volume":"137","author":"Di Buduo","year":"2021","journal-title":"Blood"},{"issue":"6","key":"2023082817051143400_bib45","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3109\/09537104.2016.1171304","article-title":"Glycans and the platelet life cycle","volume":"27","author":"Li","year":"2016","journal-title":"Platelets"},{"issue":"6","key":"2023082817051143400_bib46","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1182\/blood-2017-11-742684","article-title":"Apoptosis in megakaryocytes and platelets: the life and death of a lineage","volume":"131","author":"McArthur","year":"2018","journal-title":"Blood"},{"issue":"14","key":"2023082817051143400_bib47","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1182\/blood-2017-08-743229","article-title":"Mechanisms of platelet clearance and translation to improve platelet storage","volume":"131","author":"Edward Quach","year":"2018","journal-title":"Blood"},{"issue":"3","key":"2023082817051143400_bib48","doi-asserted-by":"crossref","first-page":"750","DOI":"10.3324\/haematol.2021.279689","article-title":"GNE-related thrombocytopenia: evidence for a mutational hotspot in the ADP\/substrate domain of the GNE bifunctional enzyme","volume":"107","author":"Bottega","year":"2021","journal-title":"Haematologica"},{"issue":"24","key":"2023082817051143400_bib49","doi-asserted-by":"crossref","first-page":"477","DOI":"10.21037\/atm.2018.10.45","article-title":"Congenital disorders of glycosylation","volume":"6","author":"Chang","year":"2018","journal-title":"Ann Transl Med"},{"issue":"6","key":"2023082817051143400_bib50","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1080\/09537104.2019.1667497","article-title":"Megakaryocyte polyploidization: role in platelet production","volume":"31","author":"Vainchenker","year":"2020","journal-title":"Platelets"},{"issue":"6","key":"2023082817051143400_bib51","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1083\/jcb.147.6.1299","article-title":"Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes","volume":"147","author":"Italiano","year":"1999","journal-title":"J\u00a0Cell Biol"},{"issue":"13","key":"2023082817051143400_bib52","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1182\/blood-2005-06-2204","article-title":"Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes","volume":"106","author":"Patel","year":"2005","journal-title":"Blood"},{"issue":"9","key":"2023082817051143400_bib53","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1111\/jth.14544","article-title":"New insights into cytoskeletal remodeling during platelet production","volume":"17","author":"Ghalloussi","year":"2019","journal-title":"J\u00a0Thromb Haemost"},{"issue":"1","key":"2023082817051143400_bib54","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10974-019-09514-0","article-title":"Actin\u2013tropomyosin distribution in non-muscle cells","volume":"41","author":"Manstein","year":"2020","journal-title":"J\u00a0Muscle Res Cell Motil"},{"issue":"6","key":"2023082817051143400_bib55","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1111\/jth.13318","article-title":"Cdc42-dependent F-actin dynamics drive structuration of the demarcation membrane system in megakaryocytes","volume":"14","author":"Antkowiak","year":"2016","journal-title":"J\u00a0Thromb Haemost"},{"issue":"4","key":"2023082817051143400_bib56","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3109\/09537104.2010.547960","article-title":"Megakaryocytes derived from patients with the classical form of Bernard-Soulier syndrome show no ability to extend proplatelets in\u00a0vitro","volume":"22","author":"Balduini","year":"2011","journal-title":"Platelets"},{"issue":"4","key":"2023082817051143400_bib57","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/S0301-472X(02)00774-9","article-title":"Absence of GPIb\u03b1 is responsible for aberrant membrane development during megakaryocyte maturation: Ultrastructural study using a transgenic model","volume":"30","author":"Poujol","year":"2002","journal-title":"Exp Hematol"},{"issue":"6","key":"2023082817051143400_bib58","doi-asserted-by":"crossref","first-page":"800","DOI":"10.3324\/haematol.2008.001032","article-title":"Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome","volume":"94","author":"Strassel","year":"2009","journal-title":"Haematologica"},{"issue":"7","key":"2023082817051143400_bib59","first-page":"402","article-title":"Ultrastructure of platelets in Bernard-Soulier syndrome","volume":"50","author":"Maldonado","year":"1975","journal-title":"Mayo Clin Proc"},{"issue":"9","key":"2023082817051143400_bib60","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1055\/s-0039-1693409","article-title":"Study of Bernard-Soulier syndrome megakaryocytes and platelets using patient-derived induced pluripotent stem cells","volume":"119","author":"Mekchay","year":"2019","journal-title":"Thromb Haemost"},{"issue":"22","key":"2023082817051143400_bib61","doi-asserted-by":"crossref","first-page":"5928","DOI":"10.1182\/blood-2011-07-365601","article-title":"Thrombocytopenia resulting from mutations in filamin A can be expressed as an isolated syndrome","volume":"118","author":"Nurden","year":"2011","journal-title":"Blood"},{"issue":"1","key":"2023082817051143400_bib62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/09537104.2011.654004","article-title":"New insights into the versatile roles of platelet FlnA","volume":"24","author":"Falet","year":"2013","journal-title":"Platelets"},{"issue":"8","key":"2023082817051143400_bib63","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1074\/jbc.M413590200","article-title":"Filamin A binding stabilizes nascent glycoprotein Ib\u03b1 trafficking and thereby enhances its surface expression","volume":"280","author":"Feng","year":"2005","journal-title":"J\u00a0Biol Chem"},{"issue":"8","key":"2023082817051143400_bib64","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1182\/blood-2006-03-009449","article-title":"Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia","volume":"108","author":"Nurden","year":"2006","journal-title":"Blood"},{"issue":"6","key":"2023082817051143400_bib65","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1182\/blood.V93.6.1951.406a33_1951_1958","article-title":"Influence of monoclonal antiplatelet glycoprotein antibodies on in\u00a0vitro human megakaryocyte colony formation and proplatelet formation","volume":"93","author":"Takahashi","year":"1999","journal-title":"Blood"},{"issue":"1","key":"2023082817051143400_bib66","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1042\/CBI20110383","article-title":"Fibronectin promotes proplatelet formation in the human megakaryocytic cell line UT-7\/TPO","volume":"36","author":"Kawaguchi","year":"2012","journal-title":"Cell Biol Int"},{"issue":"7","key":"2023082817051143400_bib67","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3324\/haematol.2016.161562","article-title":"A\u00a0new path to platelet production through matrix sensing","volume":"102","author":"Abbonante","year":"2017","journal-title":"Haematologica"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/141\/4\/406\/2074998\/blood_bld-2022-016995-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/141\/4\/406\/2074998\/blood_bld-2022-016995-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T17:05:41Z","timestamp":1693242341000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/141\/4\/406\/493253\/Novel-variants-in-GALE-cause-syndromic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":67,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,1,26]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2022016995","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]}}}