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Abstract：
Gray platelet syndrome (GPS) is a rare platelet storage pool disorder associated with a marked decrease or absence of platelet α-granules and their contents. It is characterized clinically by mild to moderate bleeding; moderate macrothrombocytopenia with large, agranular platelets; splenomegaly; and bone marrow fibrosis. Electron microscopy confirms markedly reduced or absent α-granules in platelets and megakaryocytes. The classic description of GPS is caused by homozygous mutations in NBEAL2 (neurobeachinlike 2).
A 28-year-old Hispanic man with a history of easy bruising and occasional episodes of epistaxis sought treatment for pancytopenia and splenomegaly. Peripheral blood smear and bone marrow analysis, electron microscopy, and next-generation sequencing were performed.
Large and agranular platelets were present in the peripheral blood. There was bone marrow fibrosis. Electron microscopy of the platelets showed absence of α-granules. Next-generation sequencing revealed a germline apparently homozygous nonsense variant in the NBEAL2 gene: c.5674C>T, p.Gln1892X (p.Q1829X).
The differential diagnosis of GPS includes a myeloid neoplasm such as myelodysplastic syndrome with bone marrow fibrosis. The availability of diagnostic genetic panels for hereditable platelet disorders can assist in the recognition of GPS and other platelet disorders. We also describe a previously unreported pathogenic germline homozygous nonsense variant in the NBEAL2 gene: c.5674C>T, p.Gln1892X (p.Q1829X) in a patient with GPS.
A 28-year-old Hispanic man with a history of easy bruising and occasional episodes of epistaxis sought treatment for pancytopenia and splenomegaly. Peripheral blood smear and bone marrow analysis, electron microscopy, and next-generation sequencing were performed.
Large and agranular platelets were present in the peripheral blood. There was bone marrow fibrosis. Electron microscopy of the platelets showed absence of α-granules. Next-generation sequencing revealed a germline apparently homozygous nonsense variant in the NBEAL2 gene: c.5674C>T, p.Gln1892X (p.Q1829X).
The differential diagnosis of GPS includes a myeloid neoplasm such as myelodysplastic syndrome with bone marrow fibrosis. The availability of diagnostic genetic panels for hereditable platelet disorders can assist in the recognition of GPS and other platelet disorders. We also describe a previously unreported pathogenic germline homozygous nonsense variant in the NBEAL2 gene: c.5674C>T, p.Gln1892X (p.Q1829X) in a patient with GPS.
摘要：
灰色血小板综合征（GPS）是一种罕见的血小板储存池疾病，与血小板α颗粒及其含量的显着减少或缺乏有关。临床表现为轻度至中度出血；中度大血小板减少，球状血小板；脾肿大；骨髓纤维化。电子显微镜证实血小板和巨核细胞中α-颗粒显著减少或缺失。GPS的经典描述是由NBEAL2（神经beachinlike2）中的纯合突变引起的。
一名28岁的西班牙裔男子，有容易瘀伤和偶尔发作鼻出血的病史，他寻求治疗全血细胞减少症和脾肿大。外周血涂片和骨髓分析，电子显微镜，并进行了下一代测序。
外周血中存在大的和颗粒状的血小板。有骨髓纤维化。血小板的电子显微镜检查显示不存在α-颗粒。下一代测序揭示了NBEAL2基因中明显纯合的无义变体：c.5674C>T，p.Gln1892X（p.Q1829X)。
GPS的鉴别诊断包括骨髓性肿瘤，如骨髓增生异常综合征伴骨髓纤维化。遗传性血小板疾病的诊断遗传小组的可用性可以帮助识别GPS和其他血小板疾病。我们还描述了NBEAL2基因中以前未报道的致病性种系纯合无义变体：c.5674C>T，p.Gln1892X（p.Q1829X）在有GPS的患者中。
一名28岁的西班牙裔男子，有容易瘀伤和偶尔发作鼻出血的病史，他寻求治疗全血细胞减少症和脾肿大。外周血涂片和骨髓分析，电子显微镜，并进行了下一代测序。
外周血中存在大的和颗粒状的血小板。有骨髓纤维化。血小板的电子显微镜检查显示不存在α-颗粒。下一代测序揭示了NBEAL2基因中明显纯合的无义变体：c.5674C>T，p.Gln1892X（p.Q1829X)。
GPS的鉴别诊断包括骨髓性肿瘤，如骨髓增生异常综合征伴骨髓纤维化。遗传性血小板疾病的诊断遗传小组的可用性可以帮助识别GPS和其他血小板疾病。我们还描述了NBEAL2基因中以前未报道的致病性种系纯合无义变体：c.5674C>T，p.Gln1892X（p.Q1829X）在有GPS的患者中。
