Supplementary Material for: Importance of Genetic Diagnostics in Adult-Onset Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of podocyte and glomerulus injury. FSGS can be primary and secondary to other diseases or due to a genetic cause. Strikingly, genetic causes for adult-onset FSGS are often overlooked, likely because identifying patients with genetic forms of FSGS based on clinical presentation and histopathology is difficult. Yet diagnosing genetic FSGS does not only have implications for prognostication and therapy but also for family and family planning. In this case series, we present 3 adult patients who presented with advanced renal disease with the histological picture of FSGS and proved to have a genetic cause of the disease, namely, variants in INF2, COL4A4 and HNF1B, respectively. We show the possibilities of identifying genetic FSGS based on clinical clues of a positive family history, early age at onset of disease, and/or severe therapy-resistant disease. We discuss ways to select the method of genetic testing for individual patients. Finally, we examine how the judicious use of genetic investigations can obviate potential harmful diagnostic procedures and direct clinical decisions in patients and their relatives.

局灶节段性肾小球硬化症（focal segmental glomerulosclerosis, FSGS）是一种以足细胞和肾小球损伤为特征的组织病理学表型。FSGS可分为原发性、继发性（继发于其他疾病）或由遗传因素导致。值得注意的是，成人起病的FSGS遗传病因常被忽视，这可能是因为仅通过临床表现和组织病理学特征难以甄别出遗传性FSGS患者。然而，确诊遗传性FSGS不仅对患者的预后评估与治疗决策具有重要意义，同时也关乎患者家族及计划生育规划。在本病例系列研究中，我们报告了3例成人患者：他们均表现为进展性肾病，组织病理学符合FSGS特征，后经证实其致病原因为遗传变异，分别对应INF2、COL4A4及HNF1B基因变异。本研究阐明了如何通过阳性家族史、早发性发病及/或难治性重症肾病等临床线索来识别遗传性FSGS患者。我们还探讨了针对个体患者选择合适基因检测方法的可行路径。最后，本文分析了合理运用基因检测如何规避潜在有害的诊断操作，并为患者及其亲属的临床决策提供指导。