Clinical and genetic spectrum of factor XII deficiency in the Han population of East China

doi:10.1186/s13023-024-03404-6

科研成果详情

题名	Clinical and genetic spectrum of factor XII deficiency in the Han population of East China
作者	Xu, Fei1; Qin, Langyi1; Zou, Anqing1; Hou, Lingling1; Wang, Mingshan1; Chen, Bile2
发表日期	2024-10-09
发表期刊	Orphanet Journal of Rare Diseases 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Hemorrhagic Factor XII deficiency F12 gene Mutation Thrombophilias
其他关键词	COAGULATION-FACTOR-XII ; PATIENT ; THROMBOSIS ; RISK
摘要	Background Factor XII (FXII or F12) deficiency is a rare inherited disorder, typically lacking haemorrhagic symptoms. There is limited literature exists on FXII deficiency and mutations within the Chinese population. This study aimed to characterize the spectrum of F12 gene mutations in a Chinese cohort and to investigate the relationship between FXII mutations and clinical phenotypes. Methods Genetic and clinical data from 51 unrelated probands with FXII deficiency, along with their families, were meticulously collected and analysed. Results Genetic analysis revealed that 94.1% of probands carried genetic defects, with 29 mutations pinpointed in the F12 gene. Of these, 18 mutations were previously reported for the first time by our research group, including c.303_304delCA, c.1078G > A, c.1285 C > T, among others. Of the mutations, 17 are missense, constituting 58.6% of the total. Additionally, 11 are deletions or insertions, of which 8 result in frameshifts, while the remaining one is a nonsense mutation. These mutations were predominantly concentrated in two crucial regions: the catalytic domain and the kringle domain. The most frequently observed mutations were c.1681G > A, closely followed by c.1561G > A and c.1078G > A, indicating a dominance among these mutations. Additionally, a prevalent polymorphism at position 46 was observed in the majority of probands, with 47.1% having the 46T/T genotype and 13.7% having the 46 C/T genotype, which may potentially impact FXII activity. The broad spectrum of asymptomatic FXII deficiency observed within the Han population of East China. Conclusions We speculate on the potential impact of recurrent mutations on the efficacy of new drugs being developed to target FXII for thrombosis prevention and treatment. Furthermore, it is important to explore their influence on FXII-related pathways beyond the activation of the contact pathway in the coagulation cascade.
资助项目	Wenzhou Basic Medical and Health Science and Technology Project
出版者	BMC
ISSN	1750-1172
EISSN	1750-1172
卷号	19 期号:1
DOI	10.1186/s13023-024-03404-6
页数	8
WOS类目	Genetics & Heredity ; Medicine, Research & Experimental
WOS研究方向	Genetics & Heredity ; Research & Experimental Medicine
WOS记录号	WOS:001337103900001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39385199
SCOPUSEID	2-s2.0-85205987785
通讯作者地址	[Chen, Bile]Wenzhou Med Univ, Affiliated Hosp 1, Dept Blood Transfus, Wenzhou, Peoples R China.
Scopus学科分类	Genetics (clinical);Pharmacology (medical)
SCOPUS_ID	SCOPUS_ID:85205987785
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220798
专题	附属第一医院附属第一医院_检验科附属第一医院_输血科
通讯作者	Chen, Bile
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Dept Lab Med, Key Lab Clin Lab Diag & Translat Res Zhejiang Prov, Wenzhou 325015, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Dept Blood Transfus, Wenzhou, Peoples R China
第一作者单位	附属第一医院; 检验科
通讯作者单位	附属第一医院; 输血科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Xu, Fei,Qin, Langyi,Zou, Anqing,et al. Clinical and genetic spectrum of factor XII deficiency in the Han population of East China[J]. Orphanet Journal of Rare Diseases,2024,19(1).
APA	Xu, Fei, Qin, Langyi, Zou, Anqing, Hou, Lingling, Wang, Mingshan, & Chen, Bile. (2024). Clinical and genetic spectrum of factor XII deficiency in the Han population of East China. Orphanet Journal of Rare Diseases, 19(1).
MLA	Xu, Fei,et al."Clinical and genetic spectrum of factor XII deficiency in the Han population of East China".Orphanet Journal of Rare Diseases 19.1(2024).