Phenotype-Genotype Correlations in Three Different Cases of Adult-Onset Genetic Focal Segmental Glomerulosclerosis

• Published in: International journal of molecular sciences Vol. 24; no. 24; p. 17489
• Main Authors: Kalmár, Tibor, Turkevi-Nagy, Sándor, Bitó, László, Kaiser, László, Maróti, Zoltán, Jakab, Dániel, Letoha, Annamária, Légrády, Péter, Iványi, Béla
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.12.2023
• Subjects: ACTN4 gene; Antihypertensives; Autopsies; Biopsy; CLCN5 gene; COL4A5 gene; Congenital diseases; Family medical history; Fetuses; genetic FSGS; Genetic testing; Hypertension; Kidney diseases; Morphogenesis; Mutation; PAX2 gene; Pregnancy; proteinuria; Ultrasonic imaging; PAX2 gene; CLCN5 gene; COL4A5 gene; proteinuria; renal biopsy; ACTN4 gene; genetic FSGS
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242417489

This study highlights the importance of a combined diagnostic approach in the diagnosis of rare diseases, such as adult-onset genetic FSGS. We present three adult patient cases evaluated with kidney biopsy for proteinuria, chronic kidney disease, and hypertension, which were suggestive of adult-onset genetic FSGS. Renal biopsy samples and formalin-fixed, paraffin-embedded fetal kidneys were evaluated using standard light microscopical stainings, direct immunofluorescence on cryostat sections, and electron microscopy. Clinical exome sequencing was performed for each case, and 45 FSGS-related genes were analyzed. Identifying mutations in the , , and genes have prompted a re-evaluation of the previous histopathological examinations. The mutation led to a thinner nephrogenic zone and decreased number of glomeruli, resulting in oligohydramnios during fetal development and oligomeganephronia and adaptive focal-segmental glomerulosclerosis in adulthood. The mutation caused distinct electron-dense aggregates in podocyte cell bodies, while the mutation led to segmental sclerosis of glomeruli with marked interstitial fibrosis and tubular atrophy. The identification of specific mutations and their histopathological consequences can lead to a better understanding of the disease and its progression, as well as potential treatment options.