Frequency and pathohistological characteristics of focal segmental glomerulosclerosis combined with thin basement membranes nephropathy

Mutacije gena odgovornih za sintezu α3, α4 i α5 lanaca kolagena IV uzrokuju spektar poremećaja, od nefropatije tankih glomerularnih bazalnih membrana (TBMN) do X vezanih i autosomnih oblika Alportovog sindroma (AS). Kod određenog broja pacijenata s TBMN-om se primijetilo da s vremenom bolest progredira u kronično bubrežno zatajenje (CRF) uslijed nastanka fokalne segmentalne glomeruloskleroze (FSGS). Zbog toga sve više raste interes za istraživanje povezanosti FSGS-a i navedenih mutacija. Kako je TBMN autosomno dominantni poremećaj uzrokovan mutacijom gena za α3 i/ili α4 lance kolagena IV, nije jasno jesu li neke druge mutacije na istim genima odgovorne za sekundarnu pojavu FSGS-a kod pacijenata s TBMN-om ili se radi o nekoj drugoj, za sada nepoznatoj, mutaciji drugih gena. U sklopu projekta ''Genotip-fenotip korelacija u Alportovom sindromu i nefropatiji tankih glomerularnih bazalnih membrana'', provedeno je retrospektivno istraživanje 30 pacijenata s dijagnozom FSGS-a i nalazom TBMN-a na elektronskoj mikroskopiji (EM). Cilj ovog istraživanja bio je utvrditi prisutnost poremećaja ekspresije α3, α4 i α5 lanaca kolagena IV na imunohistokemiji kod pacijenata s dijagnozom FSGS-a i TBMN-a. S obzirom da su svi analizirani uzorci imali uredne obrasce imunohistokemijskog bojanja lanaca kolagena IV, ne možemo imunohistokemijski utvrditi da je u analiziranim slučajevima FSGS posljedica mutacija gena za lance kolagena IV. Tome u prilog ide i činjenica da niti u jednom slučaju nije bilo pozitivne obiteljske anamneze za AS ili TBMN. Stoga je u analiziranih pacijenata potrebno provesti dodatno genetsko testiranje na mutacije za α3, α4 i α5 lance kolagena IV, što je i idući cilj spomenutog projekta.Recent research shows that mutations of genes indispensable for collagen IV chains synthesis cause a spectrum of disease, ranging from thin basement membrane nephropathy (TBMN) to X-linked and autosomal forms of Alport's syndrome (AS). It was noticed that some patients with TBMN at later age progress to chronic renal failure (CRF) due to the development of focal segmental glomerulosclerosis (FSGS). Therefore the interest in researching the association between FSGS and listed mutations is growing. Since TBMN is an autosomal dominant disorder caused by mutations of genes for α3 and α4 chains of collagen IV, it is not clarified wheter secondary development of FSGS in patients with TBMN is caused by some other mutations of those genes or some other, yet unknow, mutation of other genes. As part of the project ''Genotype-Phenotype correlation in Alport's syndrome and thin basement membrane nephropathy'', we performed a retrospective research of 30 patients with diagnosis of FSGS and finding of TBMN on electron microscopy (EM). The aim of this study is to affirm the irregular expression of α3, α4 and α5 chains of collagen IV on imunohistochemistry in patients with diagnosis of FSGS and TBMN. Since all samples have neat patterns of immunohistochemical staining of collagen IV chains, it cannot be established with certainty that in all cases was FSGS the result of mutations of genes for collagen IV chains. This is also supported by the fact that in none of the cases was family history positive for AS or TBMN. Therefore, the additional genetic testing for mutations of genes for α3, α4 and α5 chains of collagen IV is also required, which is the next step of the mentioned project