Case report: a novel heterozygous COL4A4 mutation causing autosomal dominant Alport syndrome

Abstract Background Autosomal Dominant Alport Syndrome (ADAS) is a rare genetic disorder caused by mutations in the COL4A3 , COL4A4, or COL4A5 genes. ADAS often presents with proteinuria and hematuria, and while progressive renal insufficiency can develop, it typically progresses more slowly compared to other forms of Alport syndrome. Due to the absence of extrarenal manifestations, such as sensorineural hearing loss or ocular abnormalities, ADAS is frequently misdiagnosed or underdiagnosed. Here, we report a novel heterozygous COL4A4 mutation in a patient with ADAS to raise awareness of this disease and emphasize the importance of genetic testing in unexplained kidney disease cases. Case presentation A 55-year-old woman presented with persistent proteinuria detected over 10 months. Her clinical history was significant for hypertension. Laboratory tests revealed proteinuria (680 mg/24 h) and hematuria. A renal biopsy showed mild mesangial proliferation and extensive glomerular basement membrane thinning. Genetic testing identified a novel heterozygous missense mutation in the COL4A4 gene (c.913G > C, p.Gly305Arg), which was also present in her son. The patient’s diagnosis was confirmed as ADAS. Conclusions This case highlights the importance of considering ADAS in patients with unexplained proteinuria and hematuria, even in the absence of family history or extrarenal symptoms. Early diagnosis through renal biopsy and genetic testing is crucial for proper management. The identification of this novel COL4A4 mutation expands the known mutational spectrum and emphasizes the need for increased clinical awareness to prevent misdiagnosis and ensure timely intervention.