| Autor: |
Giger Seu, Katie, Trump, Lisa, Emberesh, Sana, Lorsbach, Robert B., Johnson, Clarissa E., Meznarich, Jessica, Underhill, Hunter, Sakthivel, Haripriya, Niss, Omar, Nortman, Shannon, Blanc, Lionel, Zhang, Wenying, Lutzko, Carolyn, Kalfa, Theodosia A. |
| Zdroj: |
Blood; November 2019, Vol. 134 Issue: 1, Number 1 Supplement 1 p339-339, 1p |
| Abstrakt: |
The Congenital Dyserythropoietic Anemia Registry (CDAR, ClinicalTrials.gov Identifier: NCT02964494) was created to investigate the natural history, biology, and molecular pathogenetic mechanisms of CDA. To date, there are 6 genes known to cause CDA (CDAN1, C15orf41, SEC23B, KIF23, KLF1, GATA1). However, 57% of patients registered in CDAR so far (17 out of 33 patients) have an unidentified genetic cause. We have utilized whole exome sequencing (WES) in family-trio design to search for novel candidate gene mutations that may be responsible for the disease. Three unrelated patients with dyserythropoiesis, hemolytic anemia, and neurodevelopmental delay were found to have missense mutations in the gene VPS4Awhich encodes an ATPase that participates with the ESCRT III machinery in endosomal vesicle trafficking, centrosome localization, and the abscission step of cytokinesis. It has been shown to play an essential role in division of HeLa cells in vitro where it concentrates at the spindle poles during mitosis and at the midbody during cytokinesis. The aim of this work is to validate the pathogenetic role of these VPS4Avariants in CDA and further investigate the role of VPS4A in erythropoiesis. |
| Databáze: |
Supplemental Index |
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