Torra Roser, Barros Xoana, Díaz-Encarnación Montserrat, Fayos Leonor, Furlano Mónica, Pilco Melissa, Pybus Marc, Shabaka Amir, Viera Elizabeth, Ars Elisabet
Nephrology Department, Fundació Puigvert, Institut de Recerca Sant Pau (IR-Sant Pau), Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. RICORS2040.
Molecular Biology Laboratory, Fundació Puigvert, Institut de Recerca Sant Pau (IR-Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain. RICORS2040.
Clin Kidney J. 2025 Feb 13;18(3):sfaf044. doi: 10.1093/ckj/sfaf044. eCollection 2025 Mar.
This review discusses the significance of genetics in diagnosing glomerular diseases. Advances in genetic testing, particularly next-generation sequencing, have improved the accessibility and accuracy of diagnosing monogenic diseases, allowing for targeted gene panels and whole-exome/genome sequencing to identify genetic variants associated with glomerular diseases. Key indicators for considering a genetic cause include the age of onset, extrarenal features, family history, and inconclusive kidney biopsy results. Early-onset diseases, for instance, have a higher likelihood of being genetically caused, while extrarenal manifestations can also suggest an underlying genetic condition. A thorough family history can reveal patterns of inheritance that point to monogenic causes, although complexities like incomplete penetrance, skewed X inactivation and mosaicism can complicate the assessment. Also, autosomal recessive conditions imply asymptomatic parents, making genetic suspicion less likely, while mutations can occur without any family history, further obscuring genetic assessment. Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury and depletion, presenting in various forms, including primary, genetic, and secondary FSGS. Accurate classification of FSGS patients based on clinical and histological features is essential for guiding treatment decisions, optimizing therapeutic plans, avoiding unnecessary immunosuppression, and predicting relapse risk after kidney transplantation. Overall, a clinicopathological approach, enriched by genetic testing, offers a precise framework for diagnosis and management in glomerular diseases. Future directions for research and clinical practice include potential advancements in genetic testing and personalized medicine, which could further improve diagnostic precision and individualized treatment strategies.
本综述讨论了遗传学在肾小球疾病诊断中的重要性。基因检测的进展，尤其是新一代测序技术，提高了单基因疾病诊断的可及性和准确性，使得靶向基因panel以及全外显子组/基因组测序能够识别与肾小球疾病相关的基因变异。考虑遗传病因的关键指标包括发病年龄、肾外特征、家族史以及肾活检结果不明确。例如，早发型疾病由遗传因素导致的可能性更高，而肾外表现也可能提示潜在的遗传疾病。详尽的家族史能够揭示指向单基因病因的遗传模式，不过诸如不完全外显、X染色体失活偏倚以及嵌合体等复杂情况会使评估变得复杂。此外，常染色体隐性疾病意味着父母无病症表现，使得遗传方面的怀疑可能性降低，而基因突变也可能在无家族病史的情况下发生，进一步模糊了遗传评估。局灶节段性肾小球硬化（FSGS）以足细胞损伤和缺失为特征，呈现多种形式，包括原发性、遗传性和继发性FSGS。基于临床和组织学特征对FSGS患者进行准确分类对于指导治疗决策、优化治疗方案、避免不必要的免疫抑制以及预测肾移植后的复发风险至关重要。总体而言，结合基因检测的临床病理方法为肾小球疾病的诊断和管理提供了一个精确的框架。研究和临床实践的未来方向包括基因检测和个性化医疗方面的潜在进展，这可能会进一步提高诊断精度和个性化治疗策略。
