PB0578 - Molecular Mechanisms and Clinical Manifestations of Hereditary Hemorrhagic Telangiectasia

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Junwei Yuan, MA

postgraduate
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)

Co-Author(s)

JL

Jiaming Li

M.D
Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai, Shanghai, China (People's Republic)
JZ

Jialu Zhao

M.D
Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai, Shanghai, China (People's Republic)
Xi Wu, MD

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)
Yeling Lu, PhD

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China (People's Republic)
XW

Xuefeng Wang

Professor
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Shanghai, Shanghai, China (People's Republic)

Background: Hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant hereditary disease characterized by vascular malformations at skin and mucous membrane. Various studies have found that mutations of ENG and ACVRL1 are associated with HHT. However, little research has focused on the relationship between phenotypes and genotypes, which creates many difficulties for targeted prevention and early-stage therapies.

Aims: To explore the molecular mechanisms underlying HHT and its clinical manifestations to facilitate accurate clinical diagnosis.

Methods: The study recruited 20 patients with suspected HHT and conducted targeted genome sequencing to identify potential gene mutations associated with the disease. The obtained genetic results were then correlated with the clinical presentations of the patients.

Results: In 13 out of 20 single cases the method revealed a DNA change (65%). A total of 8 missense mutations were found in ACVRL1. The c.1232G>A (p.Arg411Gln) and c.A263G (p.Tyr88Cys) were recurrent in 2 dependent patients respectively. Mutations in COL3A1, ATRX, LZTR1 and NHP2 which exist simultaneously with ACVRL1 mutation in 3 patients. Three different mutations were found in ENG, including 2 missense mutation and 1 small deletion resulting in frameshift mutation. One missense mutation each in GDF2 and BMP7 was also detected in two patients respectively. Besides, no mutation was detected in the other 7 cases. Patients with the HHT1 had a 33% prevalence of pulmonary artery malformations, while the number decreased to 25% in patients with HHT2. Patients with HHT exhibit a significant elevation in vWF antigen and activity. Compared to HHT patients without thrombotic complications, those presenting with thrombotic phenotypes exhibit a marked increase in both FVIII factor and vWF activity, achieving statistical significance.

Conclusion(s): The correlation between gene mutations and clinical phenotypes reinforces the importance of genetic diagnosis in guiding precise clinical management and therapeutic interventions for patients with HHT.