Red Blood Cells and Haematopoietic Disorders (Rare Anaemias Unit), Josep Carreras Institute for Leukaemia Research (IJC), Badalona (Barcelona), Spain.
Medicine Department, University of Barcelona, Catalonia, Spain.
Int J Hematol. 2021 Feb;113(2):163-174. doi: 10.1007/s12185-020-03010-9. Epub 2020 Oct 19.
Hereditary red blood cell (RBC) membranopathies are characterized by mutations in genes encoding skeletal proteins that alter the membrane complex structure. Hereditary spherocytosis (HS) is the most common inherited RBC membranopathy leading to hereditary hemolytic anemia with a worldwide distribution and an estimated prevalence, in Europe, of about 1:2000 individuals. The recent availability of targeted next generation sequencing (t-NGS) and its combination with RBC deformability measured with a laser-assisted optical rotational ektacytometer (LoRRca) has demonstrated to be the most powerful contribution to lower the percentage of hereditary hemolytic anemia undiagnosed cases. In order to know the kind and frequency of RBC membrane mutations in our geographical area (Catalonia) and to better understand their pathophysiology, 42 unrelated, non-transfusion-dependent (NTD) patients with hereditary hemolytic anemia have been studied by combining t-NGS and LoRRca. The osmoscan module of LoRRca provides three rheological profiles that reflect the maximal deformability (EImax), osmotic fragility (Omin), and hydration state (Ohyper) of RBCs and contribute to a better understanding of the contribution RBC rheology to the severity of anemia. From the 42 patients studied, 37 were suspected to be a RBC membrane defect due to phenotypic characteristics and abnormal RBC morphology and, from these, in 31 patients (83.8% of cases) the mutation was identified by t-NGS. No definite diagnosis was achieved in 11 patients (26.2% of cases), including 6 out of 37 cases, with suspected membranopathy, and 5 with unclassifiable HHA. In all these undiagnosed patients, the existence of hemoglobinopathy and/or enzymopathy was ruled out by conventional methods.
遗传性红细胞（RBC）膜病变的特征是编码骨骼蛋白的基因突变，这些突变改变了膜复合物的结构。遗传性球形红细胞增多症（HS）是最常见的遗传性 RBC 膜病变，导致遗传性溶血性贫血，具有世界性分布，在欧洲的估计患病率约为每 2000 人中有 1 例。最近，靶向下一代测序（t-NGS）的可用性及其与使用激光辅助光旋转式 ektacytometer（LoRRca）测量的 RBC 变形性相结合，已被证明是降低未确诊遗传性溶血性贫血病例百分比的最有力贡献。为了了解我们所在地区（加泰罗尼亚）的 RBC 膜突变的种类和频率，并更好地了解其病理生理学，我们通过结合 t-NGS 和 LoRRca 研究了 42 例非输血依赖（NTD）遗传性溶血性贫血的无关患者。LoRRca 的渗透扫描模块提供了三个流变学谱，反映了 RBC 的最大变形性（EImax）、渗透脆性（Omin）和水合状态（Ohyper），有助于更好地了解 RBC 流变学对贫血严重程度的贡献。在研究的 42 例患者中，有 37 例由于表型特征和异常 RBC 形态而怀疑存在 RBC 膜缺陷，其中 31 例（83.8%的病例）通过 t-NGS 鉴定出突变。在 11 例患者（26.2%的病例）中未明确诊断，包括 37 例疑似膜病变患者中的 6 例和 5 例无法分类的 HHA 患者。在所有这些未确诊的患者中，通过常规方法排除了血红蛋白病和/或酶病的存在。
