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

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Abstract

Hereditary coagulation factor XI (FXI) deficiency is a rare bleeding disorder, but information on FXI deficiency in Taiwanese patients remains scarce. We evaluated clinical and genetic features of severe FXI deficiency patients in Taiwan. We collected clinical information and performed coagulation laboratory tests and genetic studies in ten unrelated Taiwanese families with severe FXI deficiency. FXI coagulation activity was assayed using a one-stage method. FXI antigen was determined using enzyme-linked immunosorbent assay. Underlying genetic mutations were evaluated using direct sequencing methods. Ten unrelated Taiwanese patients with hereditary FXI deficiency and variable bleeding tendencies were analyzed. Half of the patients were male. The most common bleeding manifestations were easy bruising (40%), bleeding after dental procedures (40%), and postoperative bleeding (33%). Two patients (20%) were asymptomatic. No correlation was found between bleeding manifestations and baseline FXI levels. Three novel mutations were identified: c.1322delT p.Lys442Cysfs*8, c.599G > C p.Cys200Ser, and IVS4 c.325 + 2del124. Two common mutations, c.1107C > T p.Tyr369* (40%) and c.841C > T p.Gln281* (30%), were also found. No correlation existed between bleeding and FXI activity, highlighting the difficulty in predicting FXI deficiency-related bleeding. Three novel FXI genetic mutations and two common mutations were identified, contributing to the known spectrum of FXI deficiency-related mutations.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Changhua Christian Hospital, No. 135, Nan-Hsiao Street, Changhua, Taiwan

    Hsuan-Yu Lin, Ching-Yeh Lin & Ming-Ching Shen

  2. Department of Laboratory Medicine, National Taiwan University Hospital, No.1, Changde Street, Zhongzheng District, Taipei, Taiwan

    Mei-Hua Hung & Ming-Ching Shen

  3. Department of Laboratory Medicine, Changhua Christian Hospital, No. 135, Nan-Hsiao Street, Changhua, Taiwan

    Su-Feng Kuo & Jen-Shiou Lin

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  1. Hsuan-Yu Lin
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  2. Ching-Yeh Lin
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  3. Mei-Hua Hung
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  4. Su-Feng Kuo
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  5. Jen-Shiou Lin
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Contributions

Ming-Ching Shen designed the research and supervised the study. Hsuan-Yu Lin analyzed the data, interpreted the data, and wrote the paper. Ching-Yeh Lin gathered the data. Mei-Hua Hung performed experiments. Su-Feng Kuo performed experiments and measured FXI Ag levels. Jen-Shiou Lin analyzed and interpreted the experiment results.

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Correspondence to Ming-Ching Shen.

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Lin, HY., Lin, CY., Hung, MH. et al. Characterization of hereditary factor XI deficiency in Taiwanese patients: identification of three novel and two common mutations. Int J Hematol 112, 169–175 (2020). https://doi.org/10.1007/s12185-020-02883-0

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  • DOI: https://doi.org/10.1007/s12185-020-02883-0

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