PB0563 - Clinical manifestation and mutation spectrum of 39 unrelated patients with factor V deficiency in the Chinese population

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Haoyang Wu

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

Co-Author(s)

XX

Xiaoling Xie

Research assistant
Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P.R. 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)
Yanyan Shao

Ph.D.
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China (People's Republic)
GX

Guanqun Xu

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

Yu Liu

B.S.
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China (People's Republic)
Liyang Zhou, PhD student in medicine

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

Qiulan Ding

Professor
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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: Congenital factor V deficiency (FVD), caused by mutations in F5, is a rare autosomal recessive bleeding disorder.

Aims: To analyze the mutation spectrum of large-scale FⅤ deficient patients and expand our understanding of the molecular basis of FVD in the Chinese population.

Methods: 39 unrelated patients with FVD were enrolled in the study and their bleeding symptoms were characterized by ISTH-BAT. FⅤ procoagulant activity (FⅤ: C) was tested and F5 genetic defects were detected by direct Sanger sequencing of F5 25 exons and the boundary sequences.

Results: Bleeding histories were present in 35 of 39 patients with bleeding scores from 0 to 14 and FⅤ: C from 0% to 18.4% (Fig1a,1b), while the bleeding scores had little correlation with the levels of FⅤ:C(R2=0.30). 1 in 3 patients with severe FⅤ deficiency (FV: C < 1%) and 3 in 19 patients with moderate (FV: C 1-5%) had normal bleeding scores ( < 4 in men and < 6 in women). Among the 39 patients,32 variations were found, 15 of which were reported for the first time (Fig2a,2b,2c). Of the 19 patients with significant bleeding scores, 12 were compound heterozygous, 5 were homozygous and 2 were heterozygous.10 of the 14 mutations found in the A1 and A2 domains were missense mutations. D96H (15.38%) and F218S (12.82%) were the two most prevalent mutations, both located in the A1 domain. 3 splice site mutations were found and 2 unrelated patients carried the large deletion (g.50226_58966del, p. Leu1262_Gln1657del), which was consistent with that previously reported in the Chinese population. All 4 mutations found in the B domain were small deletions/insertions.

Conclusion(s): Patients with identical mutations or levels of FⅤ: C can vary greatly in their bleeding symptoms and the newly discovered gene mutations greatly enriched the F5 gene mutation spectrum.