Phenotype-genotype correlations in patients with Alport syndrome from the Polish population

Alport syndrome (AS) is a rare inherited kidney disease associated with progressive renal failure and visual and hearing disorders. The purpose of this study was to find genetic variants in patients with suspected Alport syndrome from Central and Southwestern Poland and their association with the clinical course of the disease, and to evaluate the impact of Alport syndrome on pregnancy.

Initially, 90 patients with suspected Alport syndrome were evaluated by molecular-based testing. Clinical analyses, including urinalysis, evaluation of serum parameters, ultrasound, ophthalmologic, cardiovascular and audiology examination, and genetic testing were performed using next-generation sequencing and the Sanger method.

Seventy-seven patients (40.26% male; 59.74% female) with a median age of 6 years were included in the study group, after receiving a diagnosis of Alport syndrome. Twenty pathogenic/potentially pathogenic variants within the COL4A3, COL4A4 and COL4A5 genes were identified in these patients. The c.1871G > A variant in the COL4A5 gene was the most common (53.25%). Isolated hematuria was the most common initial sign of Alport syndrome (70.8%). Genetic testing confirmed Alport syndrome in 85% of symptomatic patients and in 15% of asymptomatic patients. Sensorineural hearing loss (17%) and ocular abnormalities (6%) were also detected in patients in the study group. Isolated hematuria showed a significant association with COL4A5 gene variants (p < 0.001). Genetic variants showed an association with initial clinical symptoms and age at Alport syndrome manifestation.

Regular urinalysis and genetic testing should be considered in suspected cases of Alport syndrome for rapid diagnosis and effective patient management.