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Hepatology. 2019 Feb;69(2):803-816. doi: 10.1002/hep.30200. Epub 2019 Jan 6.

DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera.

Pang P1,2,3, Hu X1,2,3, Zhou B1,2,3, Mao J1,2,3, Liang Y4, Jiang Z5, Huang M5, Liu R2, Zhang Y5, Qian J5, Liu J6, Xu J6, Zhang Y2, Zu M7, Wang Y2,4, He H2, Shan H1,2,3.

Author information

1
Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University.
2
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University.
3
Institute of Interventional Radiology, Sun Yat-sen University, Zhuhai, China.
4
BGI-Shenzhen, Shenzhen, China.
5
Department of Interventional Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
6
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
7
Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.

Abstract

Vascular malformations present diagnostic and treatment challenges. In particular, malformations of vessels to the viscera are often diagnosed late or incorrectly due to the insidious onset and deep location of the disease. Therefore, a better knowledge of the genetic mutations underlying such diseases is needed. Here, we evaluated a four-generation family carrying vascular malformations of major vessels that affect multiple organs, which we named "multiorgan venous and lymphatic defect" (MOVLD) syndrome. Genetic analyses identified an association between a mutation in DEAD-box helicase 24 (DDX24), a gene for which the function is largely unknown, and MOVLD. Next, we screened 161 patients with sporadic vascular malformations of similar phenotype to our MOVLD family and found the same mutation or one of the two additional DDX24 mutations in 26 cases. Structural modeling revealed that two of the mutations are located within the adenosine triphosphate-binding domain of DDX24. Knockdown of DDX24 expression in endothelial cells resulted in elevated migration and tube formation. Transcriptomic analysis linked DDX24 to vascular system-related functions. Conclusion: Our results provide a link between DDX24 and vascular malformation and indicate a crucial role for DDX24 in endothelial cell functions; these findings create an opportunity for genetic diagnosis and therapeutic targeting of malformations of vessels to the viscera.

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