X-Linked Alport Syndrome in girls: Clinicopathology, Genotype-phenotype analysis and Diagnostic Advantage of a5(IV) chain Staining on Paraffin section

Abstract Background X-linked Alport syndrome (XLAS) has been poorly studied in girls. The aim of this study was to investigate the clinicopathological features of XLAS in girls, and find out whether α5(IV) chain immunofluorescence staining on paraffin sections have a diagnositic advantage than on frozen sections. Methods The clinicopathological features and genotype-phenotype correlation were investigated retrospectively in 10 girls with XLAS. The expression of α5(IV) chain was compared between paraffin and frozen sections. The percentage of mosaic-positive glomeruli on paraffin sections was counted, and the correlation with proteinuria and age were evaluated. The literature on females with XLAS was reviewed. Results Among 10 girls with XLAS, 6 patients (60%) had intermittent attacks macroscopic hematuria with proteinuria or nephrotic-range proteinuria. Genotype–phenotype correlation was conducted and the results showed that the clinical manifestations of 3 girls with nonsense variants were all severe. Paraffin-embedded sections showed betterpreserved tissue architecture and more glomeruli than frozen sections. The detection rate of mosaic positive glomeruli on the paraffin sections was obviously increased from 60–100% when compared with the frozen section. The glomerular percentage of α5(IV) chain segmental deletion on the paraffin sections varied from 10.53–87.50% in different patients, and the percentage was not related with proteinuria and age. Conclusions Severe clinical manifestations can be seen in girls with XLAS, and nonsense mutant genotype may indicate severe clinical phenotypes. For girls with XLAS, α5(IV) chain staining should be done on paraffin sections to increase the detective rate of mosaic-positive glomeruli.