دورية أكاديمية
GALE variants associated with syndromic manifestations, macrothrombocytopenia, bleeding, and platelet dysfunction.
| العنوان: | GALE variants associated with syndromic manifestations, macrothrombocytopenia, bleeding, and platelet dysfunction. |
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| المؤلفون: | Marín-Quílez A; IBSAL, CIC, IBMCC, Universidad de Salamanca-CSIC, Salamanca, Spain.; Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, Murcia, Spain., Di Buduo CA; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Benito R; IBSAL, CIC, IBMCC, Universidad de Salamanca-CSIC, Salamanca, Spain., Balduini A; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Department of Biomedical Engineering, Tufts University, Medford, MA, USA., Rivera J; Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, Murcia, Spain., Bastida JM; Department of Hematology, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigación Biomédica de Salamanca (IBSAL), Universidad de Salamanca (USAL), Salamanca, Spain. |
| المصدر: | Platelets [Platelets] 2023 Dec; Vol. 34 (1), pp. 2176699. Date of Electronic Publication: 2023 Feb 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 9208117 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1369-1635 (Electronic) Linking ISSN: 09537104 NLM ISO Abbreviation: Platelets Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Informa Healthcare Original Publication: Edinburgh ; New York : Churchill Livingstone, c1990- |
| مواضيع طبية MeSH: | Galactosemias*/genetics , Thrombocytopenia*/genetics , UDPglucose 4-Epimerase*/genetics, Humans ; Galactose ; Hemorrhage |
| مستخلص: | GALE gene encodes the uridine diphosphate [UDP]-galactose-4-epimerase, which catalyzes the bidirectional interconversion of UDP-glucose to UDP-galactose, and UDP-N-acetyl-glucosamine to UDP-N-acetyl-galactosamine. In that way, GALE balances, through reversible epimerization, the pool of four sugars that are essential during the biosynthesis of glycoproteins and glycolipids. GALE -related disorder presents an autosomal recessive inheritance pattern, and it is commonly associated with galactosemia. Peripheral galactosemia generally associates with non-generalized forms or even asymptomatic presentations, while classical galactosemia may be related to complications such as learning difficulties, developmental delay, cardiac failure, or dysmorphic features. Recently, GALE variants have been related to severe thrombocytopenia, pancytopenia, and in one patient, to myelodysplastic syndrome. |
| فهرسة مساهمة: | Keywords: Bleeding; GALE; UDP-galactose 4-epimerase; platelet disorder; syndromic manifestations; thrombocytopenia, Local Abstract: [plain-language-summary] What is the context? GALE gene encodes for the UDP-Galactose 4-Epimerase, an enzyme involved in the Leloir pathway of galactose catabolism and protein glycosylation.Homozygous or compound heterozygous GALE variants associate with the disorder known as galactosemia type III.Three types of galactosemia can be distinguished: the peripheral, the intermediate, and the generalized form, which associate with different clinical symptoms and GALE genetic variants.Peripheral form is considered benign, while the intermediate and the generalized form is associated with severe and syndromic manifestations, including learning difficulties, delayed growth, sensorineural hearing loss, and early-onset cataracts, among others.What is new? In the last few years, GALE variants have been linked to hematological manifestations, such as anemia, febrile neutropenia, and severe thrombocytopenia.To date, the only GALE variants described in patients presenting hematological disorders are GALE p.Arg51Trp, p.Lys78ValfsX32, p.Val128Met, p.Thr150Met, p.Leu223Pro, and p.Gly237Asp.The thrombocytopenia observed in GALE patients is associated with reduced GPIbα and β1 integrin glycosylation and externalization to the megakaryocyte and platelet surface, disrupting the actin cytoskeleton remodeling.What is the impact? GALE is an essential protein for the correct megakaryocyte and platelet glycosylation. |
| المشرفين على المادة: | X2RN3Q8DNE (Galactose) EC 5.1.3.2 (UDPglucose 4-Epimerase) |
| تواريخ الأحداث: | Date Created: 20230227 Date Completed: 20230309 Latest Revision: 20230309 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1080/09537104.2023.2176699 |
| PMID: | 36846897 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1369-1635 |
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| DOI: | 10.1080/09537104.2023.2176699 |