Hua Baolai, Yan Xiaobo, He Bin, Shen Lianjun, Poon Man-Chiu
Department of Hematology Beijing Shijitan Hospital, Capital Medical University Beijing China.
Department of Hematology Yuebei People's Hospital affiliated to Medical College of Shantou University Shaoguan China.
Clin Case Rep. 2022 Aug 24;10(8):e6269. doi: 10.1002/ccr3.6269. eCollection 2022 Aug.
The risk factors for a family with VWD presenting with an ischemic stroke (IS) were explored. FVIII activity (FVIII:C), VWF antigen (VWF:Ag), and protein S activity were measured. Next generation sequencing (NGS) was performed targeting , , , . Sanger sequencing validation was performed on family members. The proband and his sister both had low FVIII:C (1 IU/dL) and VWF:Ag (3 IU/dL) levels, confirming the diagnosis of type 3 VWD. His father had nearly normal levels of FVIII:C (58 IU/dL) and VWF:Ag (57 IU/dL). His daughter had type 1 VWD with decreased FVIII:C (46 IU/dL) and VWF:Ag (19 IU/dL). NGS identified a heterozygous VWF c.2328delT (p.A778Lfs*23) frame shift mutation only in the proband and his sister. Another VWF missense mutation, c.6521G > T (p.C2174F), was found heterozygous in all members studied. A mutation, c.946C > T (p.R316C), previously reported to relate to ischemic stroke, was found heterozygous in the patient, his father, and his daughter. Only the proband and daughter have a slightly decreased plasma protein S level. This may be the first case with type 3 VWD with severe VWF/FVIII deficiency presented with ischemic stroke contributed to by a protein S defect.
对一个患有血管性血友病（VWD）并伴有缺血性卒中（IS）的家庭的危险因素进行了探究。检测了凝血因子VIII活性（FVIII:C）、血管性血友病因子抗原（VWF:Ag）和蛋白S活性。针对……进行了二代测序（NGS）。对家庭成员进行了桑格测序验证。先证者及其妹妹的FVIII:C（1 IU/dL）和VWF:Ag（3 IU/dL）水平均较低，确诊为3型VWD。他的父亲FVIII:C（58 IU/dL）和VWF:Ag（57 IU/dL）水平接近正常。他的女儿患有1型VWD，FVIII:C（46 IU/dL）和VWF:Ag（19 IU/dL）降低。NGS仅在先证者及其妹妹中鉴定出一个杂合的VWF c.2328delT（p.A778Lfs*23）移码突变。在所有研究的成员中均发现另一个VWF错义突变c.6521G＞T（p.C2174F）为杂合状态。在患者、其父亲和女儿中发现一个先前报道与缺血性卒中相关的……突变c.946C＞T（p.R316C）为杂合状态。只有先证者和女儿的血浆蛋白S水平略有降低。这可能是首例由蛋白S缺陷导致严重VWF/FVIII缺乏的3型VWD伴发缺血性卒中的病例。
