Characterization of hereditary factor XI deficiency in Taiwanese patients: identification of three novel and two common mutations

Lin, Hung‐Yu; Lin, Chung‐Sheng; Hung, Mei-Hua; Kuo, Su-Feng; Lin, Jaw‐Town; Shen, Ming‐Ching

doi:10.1007/s12185-020-02883-0

Cited by 2 publications

(5 citation statements)

References 30 publications

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“…Spontaneous bleeding is scarce in FXI, even at severely reduced activity levels (FXI activity < 20 IU/dl) but may present after surgery, trauma or postpartum. However, studies have shown that many patients with severe FXI deficiency do not experience abnormal bleeding even after surgery [2,12,13]. In this study, the bleeding phenotype of seven patients with severe FXI deficiency varied, although none of them had a history of spontaneous bleeding.…”

Section: Discussionmentioning

confidence: 73%

“…Rare haemorrhagic disorders with FXI deficiency are caused by inherited defects in the quality or quantity of FXI, and the incidence of these disorders is associated with race and geography [2,9,13]. The incidence of congenital FXI deficiency is reported to be 12 per million worldwide and 29.5 per million in East Asian populations [11,14].…”

Section: Discussionmentioning

confidence: 99%

“…In general, FXI deficiency is rarely associated with severe bleeding manifestations [2,10,13]. Spontaneous bleeding is scarce in FXI, even at severely reduced activity levels (FXI activity < 20 IU/dl) but may present after surgery, trauma or postpartum.…”

Section: Discussionmentioning

confidence: 99%

“…Nonsense (p. Gln281 Ã ) and frameshift (c.1325delT) mutations are the most common types in East Asian populations [11]. Therefore, patients in different regions have different hotspot mutations [12,13]. In this study, we evaluated the phenotypes and genotypes of seven unrelated patients with severe FXI deficiency and several family members in Shaanxi Province, China.…”

Section: Introductionmentioning

confidence: 99%

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Phenotype and genotype analysis of patients with severe factor XI deficiency in Shaanxi Province, China

Chen

Wang

et al. 2021

Blood Coagulation &Amp; Fibrinolysis

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Congenital coagulation factor XI (FXI) deficiency is a rare bleeding disorder with a heterogeneous haemorrhagic phenotype and various hotspot gene mutations associated with race and geography. Studies on FXI deficiency in Shaanxi Province, China, are scarce. In this study, seven patients with severe FXI deficiency and several family members were analysed. The International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was applied to assess bleeding symptoms. FXI activity was determined using a one-stage method, and the FXI antigen was measured by enzyme-linked immunosorbent assay. Targeted capture next-generation sequencing and Sanger sequencing were applied to detect FXI gene mutations. The bleeding phenotype varied, although none of the participants had a history of spontaneous bleeding. One maternal received replacement therapy during the perinatal period, one female patient presented with menorrhagia, one male patient experienced severe postoperative bleeding and others were asymptomatic. Family members with heterozygous mutations were all asymptomatic. The FXI activity of all the patients ranged from less than 1 to 3.1 IU/dl, and a synchronous decrease in the FXI antigen was observed. Two missense mutations (p. Gly350Glu and p. Cys482Trp), one nonsense mutation (p. Gln384∗) and one novel frameshift mutation (p. Ser225Phefs∗16) were detected. The bleeding manifestations and severity of severe FXI deficiency varied and were not related to its activity. Three reported mutations and one novel frameshift mutation were identified, thus extending the mutation spectrum of FXI deficiency.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phenotype and genotype analysis of patients with severe factor XI deficiency in Shaanxi Province, China

Chen

Wang

et al. 2021

Blood Coagulation &Amp; Fibrinolysis

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“…Only one patient (P33) with p.Tyr369* and p.Leu442Cysfs*8 experienced mild bleeding. Interestingly, both of these variants have been found only in the Chinese population [20][21][22].…”

Section: Recurrent Variantsmentioning

confidence: 99%

The spectrum of factor XI deficiency in Southeast China: four recurrent variants can explain most of the deficiencies

Zhang,

Qin,

et al. 2024

Orphanet J Rare Dis

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Background Factor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants. Results Of the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P < .001). Only nine patients experienced mild bleeding, including one partially defective patient and eight severely defective patients. The majority of patients were referred for preoperative screenings (n = 22) and checkups (n = 14). Genetic analysis revealed that 90% of the patients had genetic defects, with 2, 16, and 19 cases of heterozygous, homozygous, and compound heterozygous patients, respectively. Seventeen variants were detected in the F11 gene (6 novel), including eleven missense variants, four nonsense variants, and two small deletions scattered throughout the F11. Of the 11 missense variants, six have not yet been studied for in vitro expression. Protein modeling analyses indicated that all of these variants disrupted local structural stability by altering side-chain orientation and hydrogen bonds. Nine variants, consisting of three missense and six null variants, were detected with a frequency of two or more. The highest allele frequency was observed in p.Q281* (21.25%), p.W246* (17.50%), p.Y369* (12.50%), and p.L442Cfs*8 (12.50%). The former two were variants specific to East Asia, while the remaining two were southeast China-specific variants. Conclusion Our population-based cohort demonstrated that no correlation between the level of FXI activity and the bleeding severity in FXI deficiency. Additionally, the prevalence of FXI deficiency may have been underestimated. The nonsense p.Q281* was the most common variant in southeast China, suggesting a possible founder effect.

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Characterization of hereditary factor XI deficiency in Taiwanese patients: identification of three novel and two common mutations

Cited by 2 publications

References 30 publications

Phenotype and genotype analysis of patients with severe factor XI deficiency in Shaanxi Province, China

Phenotype and genotype analysis of patients with severe factor XI deficiency in Shaanxi Province, China

The spectrum of factor XI deficiency in Southeast China: four recurrent variants can explain most of the deficiencies

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