Ultrastructural and immunohistochemical findings in Alport's syndrome: A study of 108 patients from 97 Italian families with particular emphasis on COL4A5 gene mutation correlations

Gianna Mazzucco, Paola Barsotti, Andrea Onetti Muda, Mirella Fortunato, Michael Mihatsch, Laura Torri-Tarelli, Alessandra Renieri, Tullio Faraggiana, Mario De Marchi, Guido Monga

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

A total of 108 patients affected by Alport's syndrome, taken from 97 families, were enrolled in a genetic and ultrastructural study. Sixty-four families (75 patients) were X-linked, seven autosomal recessive, two autosomal dominant, five uninterpretable, and 19 sporadic. The ultrastructural features were consistent with Alport's syndrome in 66, doubtful in 20, and not significant for Alport's syndrome in 22 patients in the X-linked, sporadic, and genetically uninterpretable groups (without significant differences), as well as in the autosomal group. Mutations of the COL4A5 gene were present in 36 patients in the first three groups, without significant differences. More severe mutations were more frequently present in patients with an ultrastructural pattern consistent with Alport's syndrome. Nevertheless, there seems to be no strict correlation between mutation and ultrastructure, because a major rearrangement was found in a patient with no significant lesions, and different morphologic patterns were detected in patients belonging to the same family. Immunohistochemical investigation into 24 patients for α(IV) chains showed that both α3(IV) and α5(IV) were lacking in the glomerular basement membrane of 13 patients (five with mutations) and were expressed in another six (three with mutations and one in the autosomal group). On the contrary, in this study the retained expression of α3(IV) chain was found, despite the lack of α5(IV) in the glomerular basement membrane of five patients (two with mutation). These different patterus could be related to both the type and severity of the COL4A5 mutations. All of the ultrastructural patterns were identified in all three immunohistochemical groups. Ultrastructural features and α5(IV) chain production, even if an expression of a genetic mutation, do not strictly correlate. The combined use of analysis of collagen expression and electron microscopy made it possible to diagnose Alport's syndrome in 92% of the cohort, and therefore this approach is advisable. A multidisciplinary approach is recommended in the study of Alport's syndrome in an attempt to achieve a better diagnostic definition of and insight into the pathogenetic mechanisms.

Lingua originaleInglese
pagine (da-a)1023-1031
Numero di pagine9
RivistaJournal of the American Society of Nephrology : JASN
Volume9
Numero di pubblicazione6
Stato di pubblicazionePubblicato - giu 1998
Pubblicato esternamente

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