title: Clinical manifestations and mutation spectrum of 57 subjects with congenital factor XI deficiency in China.
abstract: Congenital factor XI (FXI) deficiency is a rare bleeding disorder with unpredictable bleeding tendency. Few studies in a large cohort have been reported regarding associations between FXI activity (FXI:C) or genotypes and bleeding symptoms currently. This study characterized clinical manifestations and mutation spectrum of 57 subjects with FXI deficiency in China. Clinical data were collected and mutations were identified by direct sequencing and determined by mRNA analysis. The result revealed bleeding symptoms were only found in 12 patients (12/57, 21.1%) with severely reduced FXI:C, and prolonged bleeding post injury/surgery as well as easy bruising were the commonest bleeding manifestations presented in respective 5 cases (5/12, 41.7%). A total number of 37 mutations were identified including 19 missense mutations, 9 nonsense mutations, 6 splice site mutations and 3 small deletions. Among them, 4 missense mutations, 5 splice mutations, 3 small deletions and a nonsense mutation were newly detected. W228*, G400V, Q263* and c.1136-4delGTTG with a total frequency of 48.3% were the most four common mutations in Chinese patients. RT-PCR analysis was carried out and confirmed that both c.596-8T>A and c.1136-4delGTTG were pathogenic due to frameshift resulting in respective truncated proteins. Our findings suggested clinical manifestations had little to do with FXI:C or genotypes, which required further study. This study, the largest investigation of FXI deficiency in China revealed that the F11 mutation spectrum of Chinese population was distinct from those of other populations earlier established.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yeling
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: qiulan_ding@126.com.
authors.forename: Qiulan
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005172:Factor XI / Q000235:genetics*; D005173:Factor XI Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D005172:Factor XI
keywords: Bleeding symptoms; F11 gene; Factor XI deficiency; Mutation spectrum; mRNA transcripts