Novel COL4A3 synonymous mutation causes Alport syndrome coexistent with immunoglobulin A nephropathy in a woman: A case report

Alport syndrome (AS) is an inherited disease of the glomerular basement membrane caused by mutations in genes encoding α3, α4, or α5 chains of type IV collagen. It manifests with hematuria or proteinuria, which is often accompanied by hearing impairments and ocular abnormalities. Histopathologically, AS shows mesangial proliferation and sometimes incidental immunoglobulin A (IgA) deposition. Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.

Herein, we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for > 2 years. This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS (ADAS) and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing, which suggested that the patient carried a novel heterozygous variation (c.888G>A:p.Gln296Gln) in the COL4A3 gene that enriches the mutation spectrum of ADAS. The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established. After one year of therapy, a significant reduction in proteinuria was observed. The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels. Renal function also maintained well during the follow-up.

Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.