Ma S Q, Bai X, Cao L J, Ma Z N, Ding Z X, Yu Z J, Jiang M
Department of hematology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou 215028, China.
National Clinical Medical Research Center of Blood Diseases, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou 215007, China.
Zhonghua Xue Ye Xue Za Zhi. 2024 Jun 14;45(6):602-605. doi: 10.3760/cma.j.cn121090-20231216-00317.
A 28-year-old woman was found to have coagulation factor Ⅷ activity (FⅧ∶C) <1% and von Willebrand factor antigen (VWF∶Ag) <1% during routine prenatal examinations. No pathogenic variation was found in the exon region of the VWF gene using next-generation sequencing. The clinical presentation of this patient does not match the clinical characteristics of type Ⅲ hemophilia [von Willebrand disease (VWD) ]; therefore, third-generation sequencing technology was used to perform whole-genome sequencing on the patient and her family members. Multiple members of the patient's paternal family carried a heterozygous variant of VPS33B, c.869G>C. The family members carrying this variant all had varying degrees of reduced VWF levels (39% -56% ). Moreover, the proband was detected with the heterozygous variant c.1474dupA in GP1BA. The ACMG and Clinvar databases determined that this variation was associated with platelet-type pseudo VWD. The decrease in VWF levels caused by heterozygous variations in VPS33B in families is the first international report, and no previous studies have reported cases of severe decrease in plasma VWF levels caused by double heterozygous variations in VPS33B and GP1BA.
一名28岁女性在常规产前检查中被发现凝血因子Ⅷ活性（FⅧ∶C）<1%，血管性血友病因子抗原（VWF∶Ag）<1%。使用二代测序在VWF基因的外显子区域未发现致病变异。该患者的临床表现与Ⅲ型血友病[血管性血友病（VWD）]的临床特征不符；因此，使用三代测序技术对该患者及其家庭成员进行全基因组测序。患者父系家族的多名成员携带VPS33B的杂合变异，c.869G>C。携带该变异的家庭成员均有不同程度的VWF水平降低（39% -56%）。此外，先证者在GP1BA中检测到杂合变异c.1474dupA。ACMG和Clinvar数据库确定该变异与血小板型假性VWD相关。家族中VPS33B杂合变异导致VWF水平降低是国际首例报道，既往无研究报道VPS33B和GP1BA双重杂合变异导致血浆VWF水平严重降低的病例。
