Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype–phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In‐depth clinical and genetic data of 60/62 children who participated in the EARLY PRO‐TECT Alport trial were analyzed. Genetic variants were interpreted according to current guidelines and criteria. Genetically solved patients with X‐linked inheritance were then classified according to the severity of their COL4A5 variant into less‐severe, intermediate, and severe groups and disease progress was compared. Almost 90% of patients were found to carry (likely) pathogenic variants and classified as genetically solved cases. Patients in the less‐severe group demonstrated a borderline significant difference in disease progress compared to those in the severe group (p = 0.05). While having only limited power according to its sample size, an obvious strength is the precise clinical and genetic data of this well ascertained cohort. As in published data differences in clinical progress were shown between patients with COL4A5 less‐severe and severe variants. Therefore, clinical and segregational data are important for variant (re)classification. Genetic testing should be mandatory allowing early diagnosis and therapy of AS.

中文翻译：

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EARLY PRO-TECT Alport 试验中儿童的精确变异解释、表型确定和基因型-表型相关性

Alport 综合征 (AS) 患者早期开始治疗可使肾功能衰竭减缓多年。基因型-表型相关性表明个体变异的位置和特征与肾脏结果和任何额外的肾脏表现相关。对参加 EARLY PRO-TECT Alport 试验的 60/62 名儿童的深入临床和遗传数据进行了分析。根据当前的指南和标准解释遗传变异。然后根据COL4A5的严重程度对基因解决的 X 连锁遗传患者进行分类将变异分为较轻、中、重三组，并对疾病进展进行比较。几乎 90% 的患者被发现携带（可能）致病变异，并被归类为基因解决的病例。与严重组相比，较轻组患者在疾病进展方面表现出临界显着差异（p = 0.05）。虽然根据其样本量只有有限的功效，但一个明显的优势是这个确定的队列的精确临床和遗传数据。正如已发表的数据所示，COL4A5患者之间的临床进展存在差异不太严重和严重的变异。因此，临床和分离数据对于变异（重新）分类很重要。基因检测应该是强制性的，以便对 AS 进行早期诊断和治疗。