Familial Focal Segmental Glomerulosclerosis With Late-Onset Presentation and R229Q/R291W Podocin Mutations

Autor(es)

Riguetti, Michelle T. P. ^[1] ; Varela, Patricia ^[2] ; Fernandes, Danilo E. ^[1] ; Polito, M. Goretti ^[1] ; Casimiro, Fernanda M. ^[2] ; Pesquero, Joao B. ^[2] ; Mastroianni-Kirsztajn, Gianna ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Nephrol, Dept Med, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biophys, Ctr Res & Mol Diagnost Genet Dis, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN GENETICS; v. 11, SEP 16 2020.
• Citações Web of Science: 0

Resumo

Introduction Pathogenic variants in different genes have been described as involved in the development of familial focal segmental glomerulosclerosis (FSGS). A more precise genotype-phenotype correlation would be helpful to better characterize the clinical and laboratorial manifestations of this disease, as well as response to treatment. We analyzed podocin (NPHS2) gene variants in 50 members of four generations of a family with late-onset presentation of glomerular disease. Results and Discussion TheNPHS2gene variants R229Q and/or R291W were detected in several individuals, and the phenotype of FSGS with progressive loss of renal function was observed in all the family members carrying both mutations simultaneously. Patients manifested ongoing proteinuria over the years and progressive loss of renal function, which in three women culminated in renal replacement therapy by the 4th decade of life. In two affected patients with nephrotic syndrome, remission was not reached by the use of corticosteroids and other immunosuppressive drugs. The R229Q variant was pathogenic only when trans-associated with specific mutations, as the R291W variant in this family. Conclusion Coexistence of the twoNPHS2variants R229Q and R291W in compound heterozygosis was a determinant of the FSGS phenotype. The presence of these variants alone in heterozygosis did not cause significant proteinuria. (AU)

• Processo FAPESP: 19/05266-5 - Pesquisa e caracterização funcional de mutações em Glomeruloesclerose segmentar e focal familiar e esporádica.
• Beneficiário: Gianna Mastroianni Kirsztajn
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/27198-8 - Estabelecimento de um centro de pesquisa genética e molecular para desafios clínicos
• Beneficiário: João Bosco Pesquero
• Modalidade de apoio: Auxílio à Pesquisa - Temático