Ma Jingyao, Chen Zhenping, Li Gang, Gu Hao, Wu Runhui
Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, P.R. China.
Exp Ther Med. 2021 Apr;21(4):360. doi: 10.3892/etm.2021.9791. Epub 2021 Feb 13.
Classic Bernard-Soulier syndrome (BSS) is a rare form of autosomal recessive disorder that is caused by mutations in the GP1BA gene that encode the GPIb-V-IX complex, a receptor of von Willebrand factor. BSS characterized by macrothrombocytopenia and excessive bleeding. The present study reports a single case (18-month Chinese girl) diagnosed with BSS. The patient suffered mild thrombocytopenia, giant platelets and normal platelet aggregation. In addition, mild bleeding and thrombocytopenia were also indicated in thirteen family members, including the proband and her father. Gene sequence analysis identified a monoallelic missense mutation in GP1BA (c.97T>A), which encodes a p.C33R substitution in the N-terminal domain of glycoprotein (GP)Ibα that may disrupt the protein structure. To the best of our knowledge, this dominant variant has not been reported previously. BSS's autosomal dominant inheritance mode is rarely identified and can be easily misdiagnosed as immune thrombocytopenia. For patients with giant platelets, thrombocytopenia and positive family history, next-generation sequencing for inherited thrombocytopenia, especially disorders that are caused by mutations in glycoprotein Ib-IX-V complex, is required.
经典的伯纳德-索利尔综合征(BSS)是一种罕见的常染色体隐性遗传病,由编码糖蛋白(GP)Ib-V-IX复合物(血管性血友病因子的一种受体)的GP1BA基因突变引起。BSS的特征是大血小板减少症和出血过多。本研究报告了一例被诊断为BSS的病例(一名18个月大的中国女孩)。该患者有轻度血小板减少、巨大血小板和正常的血小板聚集。此外,包括先证者及其父亲在内的13名家庭成员也有轻度出血和血小板减少。基因序列分析确定了GP1BA中的一个单等位基因错义突变(c.97T>A),该突变在糖蛋白(GP)Ibα的N端结构域编码一个p.C33R替代,这可能会破坏蛋白质结构。据我们所知,这种显性变异此前尚未见报道。BSS的常染色体显性遗传模式很少被识别,很容易被误诊为免疫性血小板减少症。对于有巨大血小板、血小板减少症和阳性家族史的患者,需要进行遗传性血小板减少症的二代测序,尤其是由糖蛋白Ib-IX-V复合物突变引起的疾病。