Minkov Milen, Zeitlhofer Petra, Zoubek Andreas, Kager Leo, Panzer Simon, Haas Oskar A
Department of Pediatrics, Clinic Floridsdorf, Vienna, Austria.
Faculty of Medicine, Sigmund Freud University, Vienna, Austria.
Front Pediatr. 2021 Jan 22;8:589812. doi: 10.3389/fped.2020.589812. eCollection 2020.
Bernard-Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the , or genes, which together encode the platelet surface receptor glycoprotein complex GPIb-IX-V. We report two novel heterozygous mutations in the and the genes, respectively. We analyzed the platelet glycoprotein expression by flow cytometry and screened the relevant genes for responsible mutations in two unrelated families. Flow cytometric analyses revealed the absence of CD42a (GPIX) and CD42b (GPIb) on the platelets in the two affected siblings of family 1 and a significantly reduced expression of CD42b (GPIb) in the patient of family 2. In the two siblings, we identified a known frameshift (c.1601_1602delAT) and a novel nonsense mutation (c.1036C>T) in the gene that abrogated the production of GP1bα. In the other patient, we found a novel missense mutation (c.112T>C) that was co-inherited with a common one (c.182A>G) in the gene, respectively. All analyzed heterozygous carriers were asymptomatic and had a normal GPIb-IX-V expression. The two novel and mutations reported herein increment the number of causative genetic defects in BSS.
伯纳德-索利尔综合征（BSS）是一种罕见的常染色体隐性出血性疾病，其特征为血小板体积增大和血小板减少。它是由 、 或 基因的纯合或复合杂合突变引起的，这些基因共同编码血小板表面受体糖蛋白复合物GPIb-IX-V。我们分别报告了 基因和 基因中的两个新的杂合突变。我们通过流式细胞术分析了血小板糖蛋白的表达，并在两个无关家族中筛选了相关基因以寻找致病突变。流式细胞术分析显示，在家族1的两名受影响的兄弟姐妹中，血小板上不存在CD42a（GPIX）和CD42b（GPIb），而在家族2的患者中，CD42b（GPIb）的表达显著降低。在这两名兄弟姐妹中，我们在 基因中鉴定出一个已知的移码突变（c.1601_1602delAT）和一个新的无义突变（c.1036C>T），这两个突变均导致GP1bα无法产生。在另一名患者中，我们分别发现了一个新的错义突变（c.112T>C），该突变与 基因中的一个常见突变（c.182A>G）共同遗传。所有分析的杂合携带者均无症状，且GPIb-IX-V表达正常。本文报道的两个新的 基因和 基因的突变增加了BSS致病基因缺陷的数量。
