RT期刊文章SR电子T1拓扑关系数据分析揭示了genotype-phenotype原发性纤毛运动障碍摩根富林明欧洲呼吸杂志乔和J FD欧元欧洲呼吸学会SP 2002359 10.1183/13993003.02359 -2020签证官58 2 A1 Shoemark,阿米莉亚A1 Rubbo,米菲A1勒让德,玛丽A1 Fassad,188bet官网地址马哈茂德·r·A1 Haarman埃里克·g . A1最好Sunayna A1好,厄玛:A1 Brandsma, Joost A1 Burgel, Pierre-Regis A1,贡纳A1卡尔,西沃恩·b·A1卡罗尔,玛丽A1爱德华兹,马特A1 Escudier,埃斯特尔A1欧诺瑞,伊莎贝尔A1狩猎,大卫A1 Jouvion,格里高利A1 Loebinger,米歇尔·r·A1管家,伯纳德A1 Morris-Rosendahl,黛博拉A1帕庞,Jean-Francois Parsons, Camille M. A1 Patel, Mitali P. A1 Thomas, N. Simon al thovenin, Guillaume A1 Walker, Woolf T. A1 Wilson, Robert A1 Hogg, Claire A1 Mitchison, Hannah M. A1 Lucas，原发性纤毛运动障碍(PCD)是一种异质性遗传疾病，由约50个纤毛相关基因突变引起。PCD基因型与表型的关系大多来自小病例系列，因为现有的统计方法不适用于罕见疾病。方法应用拓扑数据分析(TDA)方法研究PCD的基因型与表型关系。来自单独训练和验证队列的数据包括396个基因定义的携带PCD基因致病变异的个体。为了建立TDA模型，我们纳入了12个临床和诊断变量。tda驱动的假设随后使用传统统计学进行了检验。结果以1秒用力呼气量(FEV1) z-score衡量的疾病严重程度，CCDC39突变个体显著低于其他基因突变个体(与其他基因突变相比)，而DNAH11突变个体明显优于CCDC39突变个体;后者也报告新生儿呼吸窘迫较少。 Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis.Conclusions This large scale, multi-national study presents PCD as a syndrome with overlapping symptoms and variations in phenotype according to genotype. TDA modelling confirmed genotype–phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutation) and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations.Topological data analysis of 396 primary ciliary dyskinesia patients shows genetic mutations of worse (CCDC39), variable (DNAH5) and milder (DNAH11) effects on lung function, offering the potential for more accurately targeted disease management https://bit.ly/3oL5r64