Alport syndrome (AS) is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in COL4A3, COL4A4 or COL4A5 genes. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS).
Retrospective cohort study.
82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected.
A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families) while 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 years (95% CI, 58-73), without significant differences across sex (P=0.79), causative genes (P=0.55) or types of variant (P=0.99). 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 eGFR decline was -1.46 mL/min/1.73 m per year (-1.66 to -1.26) for the overall group, with no significant differences between ADAS genes (P=0.24).
The relatively small size of this series from a single country, potentially limiting generalizability.
ADAS patients have a wide spectrum 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.

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