: 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.
Debeh et al. (Tue,) studied this question.