Genotype-phenotype correlation and risk stratification in a cohort of 123 hereditary stomatocytosis patients
Genotype-phenotype correlation and risk stratification in a cohort of 123 hereditary stomatocytosis patients
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DOI：
10.1002/ajh.25276
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发表时间：
2018-12-01
影响因子：
12.8
通讯作者：
Iolascon, Achille
中科院分区：
文献类型：
--
作者：
Andolfo, Immacolata;Russo, Roberta;Iolascon, Achille
遗传性口细胞增多症 (HSts) 是一种广泛的溶血性贫血，其中红细胞膜阳离子通透性增加。脱水遗传性口细胞增多症是 HSt 中最常见的。它是由 PIEZO1 和 KCNN4 基因的错义突变引起的。我们描述了 2013 年至 2017 年在我们的遗传部门登记的 123 名患者。总体而言，HSt 受试者表现出大细胞性轻度贫血。我们发现 PIEZO1 是我们家族中最常见的突变基因（占谱系的 47%）。在 59.1% 的病例中，突变位于非孔蛋白结构域，而在 40.9% 的患者中，突变位于中央孔区域。对 29 名 PIEZO1 患者的基因型-表型相关性分析表明，大多数严重受影响的患者在孔结构域中携带突变，这表明这种情况的严重程度与孔特性和细胞内结构域有关，孔结构和细胞内结构域可能负责与细胞内成分的相互作用。这是第一个针对大量遗传性口细胞增多症患者的队列研究，根据对这些患者的诊断、预后和管理有用的致病基因进行分层。
Hereditary stomatocytoses (HSts) are a wide spectrum of hemolytic anemias in which the erythrocyte membrane cation permeability is increased. Dehydrated hereditary stomatocytosis is the most frequent among HSts. It is caused by missense mutations in PIEZO1 and KCNN4 genes. We described 123 patients enrolled in our Genetic Unit from 2013 to 2017. Overall HSt subjects exhibit macrocytic mild anemia. We found that PIEZO1 is the most frequent mutated gene within our families (47% of pedigrees). In 59.1% of cases the mutations localized in the nonpore protein domain, while in 40.9% of patients they localized in the central pore region. The genotype-phenotype correlation analysis on 29 PIEZO1-patients demonstrated that most of severely affected patients carried mutations in the pore domain, suggesting that the severity of this condition is related to the pore properties and intracellular domain that could be responsible of interactions with intracellular components. This is the first cohort study on a large set of hereditary stomatocytosis patients, stratified according to their causative gene useful for diagnosis, prognosis, and management of these patients.