TY - T1的拓扑关系数据分析揭示了genotype-phenotype原发性纤毛运动障碍JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02359 -2020欧元六世- 58 - 2 SP - 2002359 AU Shoemark阿米莉亚AU - Rubbo,米菲AU -勒让德,玛丽AU - Fassad,马哈茂德·r . AU - Haarman,埃里克·g . AU -最佳Sunayna AU Bon,厄玛:非盟- Brandsma Joost盟——Burgel Pierre-Regis盟——Carlsson贡纳AU -卡尔,西沃恩·b·AU -卡罗尔,玛丽AU -爱德华兹,马特AU - Escudier,埃斯特尔非盟-欧诺瑞,伊莎贝尔盟-亨特,大卫盟——Jouvion Gregory AU - Loebinger米歇尔·r . AU -管家,伯纳德AU - Morris-Rosendahl,黛博拉盟-帕庞,Jean-Francois AU - Parsons, Camille M. AU - Patel, Mitali P. AU - Thomas, N. Simon AU - Thouvenin, Guillaume AU - Walker, Woolf T. AU - Wilson, Robert AU - Hogg, Claire AU - Mitchison, Hannah M. AU - Lucas，原发性纤毛运动障碍(PCD)是由大约50个纤毛相关基因突变引起的异质性遗传疾病。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 ER -