Clinical and Genetic Features of Autosomal Dominant Alport Syndrome: A Cohort Study
Clinical and Genetic Features of Autosomal Dominant Alport Syndrome: A Cohort Study
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DOI：
10.1053/j.ajkd.2021.02.326
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发表时间：
2021-09-21
影响因子：
13.2
通讯作者：
Torra, Roser
中科院分区：
文献类型：
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作者：
Furlano, Monica;Martinez, Victor;Torra, Roser
理由和目标：Alport综合征是一种常见的遗传性肾脏疾病，约占接受肾脏替代治疗（KRT）患者的2%。它是由基因COL 4A 3、COL 4A 4或COL 4A 5中的致病性变体引起的。本研究的目的是评估常染色体显性遗传Alport综合征（ADAS）患者的临床和遗传谱。研究设计：回顾性队列研究。临床，遗传，实验室和病理学datasecolved.Observations：在COL 4A 3的致病性DNA变异被确定在107例（35个家庭），而133窝藏在COL 4A 4的致病性变异（43个家庭）。在12例患者中观察到双基因/复合遗传。总体而言，中位肾脏生存期为67年（95% CI，58-73），性别（P = 0.8）、致病基因（P = 0.6）或变异类型（P = 0.9）之间无显著差异。显微血尿是最常见的肾脏表现（92.1%），肾外表现少见。肾活检结果从正常到局灶节段性肾小球硬化。估计肾小球滤过率变化的斜率为-1.46整个组每年（-1.66至-1.26）mL/min/1.73 m（2），ADAS基因之间没有显着差异（P = 0.2）.局限性：来自单一国家的这一系列数据规模相对较小，可能限制了普遍性。ADAS患者具有广泛的临床表现，从无症状到肾衰竭，这种模式与致病基因或变异类型没有明显关系。ADAS表型的多样性导致其在临床实践中诊断不足。
Rationale & Objective: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS).Study Design: Retrospective cohort study.Setting & Participants: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected.Observations: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P = 0.8), causative genes (P = 0.6), or type of variant (P = 0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was -1.46 (-1.66 to -1.26) mL/min/1.73 m(2) per year for the overall group, with no significant differences between ADAS genes (P = 0.2).Limitations: The relatively small size of this series from a single country, potentially limiting generalizability.Conclusions: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.