Supplementary Material for: Characterization of Kidney and Liver Cystic Phenotype Associated with GANAB Using Advanced Imaging Biomarkers

Abstract: Background and Hypothesis: Monoallelic pathogenic variants in GANAB cause autosomal dominant cystic kidney and liver disease, but quantitative imaging phenotypes remain incompletely defined. Methods: We performed a retrospective study of 16 individuals with GANAB variants and available abdominal imaging. Deep learning based-cyst segmentation quantified kidney and liver volumes and cyst metrics, including height-adjusted total kidney volume (htTKV), liver volume (htTLV), cyst number (TCN), and cyst volume (htTCV). Results: Hepatic involvement was common, with polycystic liver disease present in most individuals with varying severity (liver TCN range 22 to 219). Kidney involvement was more heterogenous (htTKV range 153 to 858 mL/m; kidney TCN range 3 to 42). Individuals with kidney TCN <20 had preserved kidney function and slower annual eGFR decline (median -1.68 mL/min/1.73m2) compared with those with kidney TCN ≥20 (-2.8 mL/min/1.73 m2/year); no individual progressed to kidney failure during follow up. Hypertension occurred in 50%. Intracranial aneurysms were identified in 3 of 6 screened individuals, including two from a family with known aneurysmal disease. Conclusions: Quantitative imaging reveals a phenotypic spectrum in ADPKD-GANAB, ranging from liver-predominant cystic disease with minimal kidney involvement to a phenotype with higher kidney cyst burden and faster eGFR decline. Establishing robust genotype–phenotype relationships in this rare disease will require larger, aggregated cohorts with standardized imaging and systemic extrarenal screening.

摘要：背景与假说：GANAB基因的单等位致病变异可导致常染色体显性遗传性多囊肝肾疾病，但该疾病的定量影像学表型迄今尚未完全明确。方法：本研究回顾性分析了16例携带GANAB变异且具备腹部影像学资料的受试者。采用基于深度学习的囊肿分割算法，量化肝肾体积及囊肿相关指标，包括身高校正总肾体积（height-adjusted total kidney volume, htTKV）、身高校正总肝体积（height-adjusted total liver volume, htTLV）、囊肿总数（total cyst number, TCN）以及身高校正总囊肿体积（height-adjusted total cyst volume, htTCV）。结果：肝脏受累较为常见，多数受试者存在不同严重程度的多囊肝病，肝囊肿总数范围为22~219。肾脏受累则异质性更强，htTKV范围为153~858 mL/m，肾囊肿总数范围为3~42。与肾囊肿总数≥20的受试者相比，肾囊肿总数<20的受试者肾功能保留更佳，年估算肾小球滤过率（eGFR）下降速率更缓慢（中位数为-1.68 mL/min/1.73m²），后者中位数为-2.8 mL/min/1.73 m²/年；随访期间无受试者进展为肾衰竭。50%的受试者合并高血压。在接受筛查的6例受试者中，3例检出颅内动脉瘤，其中2例来自已知动脉瘤病史的家族。结论：定量影像学分析揭示了GANAB相关常染色体显性多囊肾病（ADPKD-GANAB）的表型谱，其范围涵盖以肝脏受累为主、肾脏累及轻微的表型，至肾囊肿负荷较高且eGFR下降更快的表型。要在这一罕见疾病中建立可靠的基因型-表型关联，需要纳入更大规模的聚合队列，并采用标准化影像学检查及系统性肾外筛查手段。