Abstract: TH-PO466
Clinical and Genetic Characteristics of INF2-Related Monogenic FSGS
Session Information
- Genetic Diseases: Glomerulopathies - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- White, Eoghan, Beaumont Hospital, Dublin, Ireland
- Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
- McAnallen, Susan Marie, Beaumont Hospital, Dublin, Ireland
- Jorge, Sofia C.a., Hospital de Santa Maria, Lisboa, Lisboa, Portugal
- Hoefele, Julia, Technische Universitat Munchen, Munchen, Bayern, Germany
- Colliou, Eloise, Centre Hospitalier Universitaire de Toulouse, Toulouse, Occitanie, France
- Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
Background
Focal segmental glomerulosclerosis (FSGS) is a histological lesion with diverse aetiologies. Although monogenic forms of FSGS are characterized by a grim clinical course, resulting in early end-stage renal disease (ESRD), they often remain underdiagnosed. Disease-causing variants in INF2 (inverted formin 2), which encodes an essential actin regulatory protein, have been identified as the most common cause of dominantly inherited FSGS; however, the disease has a highly heterogeneous clinical presentation and progression.
Methods
To describe the natural history of INF2-related FSGS, we established a INF2 research group and produced an e-survey describing the clinical outcomes (age at presentation, disease trajectory, histological diagnosis) and genetic data (exon location, and functional domains).
Results
We have received responses from 9 European centers and collected data from 53 patients (21 families), 22 (41.5%) of these cases have not previously been published. The age of initial presentation was 26.3 ± 12.8 years, with the majority of patients presenting with proteinuria and/or edema. Among the 25 patients (47.2%) who underwent kidney biopsy, FSGS accounted for 64% of the histopathologic diagnoses. Of the available data, 18 had reached end-stage kidney disease with a mean time to ESKD of 7.8 years from the presentation. Ten patients have undergone transplantation, and 8 patients had associated Charcot-Marie Tooth Neuropathy. Most families [19/22; 86.4%] had missense variants spanning exons 2 to 4 that localize to a diaphanous inhibitory domain.
Conclusion
INF2 is an increasingly recognized cause of monogenic kidney disease that can lead to ESKD and has an important impact on responses to treatment. Continued efforts are required to determine phenotype variability and disease severity of INF2-related FSGS globally.