| Title: |
Hot Spot of Complement Factor I Rare Variant p.Ile357Met in Patients With Hemolytic Uremic Syndrome. |
| Authors: |
Schwotzer, N.; Fakhouri, F.; Martins, P.V.; Delmas, Y.; Caillard, S.; Zuber, J.; Moranne, O.; Mesnard, L.; Frémeaux-Bacchi, V.; El-Sissy, C. |
| Publication Year: |
2024 |
| Collection: |
Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| Subject Terms: |
Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Atypical Hemolytic Uremic Syndrome/genetics; Complement Factor I/genetics; Mutation; Missense; Retrospective Studies; Atypical HUS; C3 glomerulopathy; CFI; Complement factor I; aHUS; p.Ile357Met |
| Description: |
Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease due to a dysregulation of the complement alternative pathway. Complement factor I (CFI) negatively regulates the alternative pathway and CFI gene rare variants have been associated to aHUS with a low disease penetrance. We report 10 unrelated cases of HUS associated to a rare CFI variant, p.Ile357Met (c.1071T>G). All patients with isolated p.Ile357Met CFI missense variant were retrospectively identified among patients included between January 2007 and January 2022 in the French HUS Registry. We identified 10 unrelated patients (70% women; median age at HUS diagnosis, 36.5 years) who carry the same rare variant p.Ile357Met in the CFI gene. Seven patients (cases 1-7) presented with aHUS in the native kidney associated with malignant hypertension in 5 patients. None received a C5 inhibitor. Two of these cases occurred in the peripartum period with complete recovery of kidney function, while 5 of these patients reached kidney failure requiring replacement therapy (KFRT). Four patients with KFRT subsequently underwent kidney transplantation. Three later developed C3 glomerulopathy in their kidney graft, but none had aHUS recurrence. Three other patients (cases 8-10) experienced de novo thrombotic microangiopathy after kidney transplantation, precipitated by various triggers. The rare CFI variant p.Ile357Met appears to be a facilitating genetic factor for HUS and for some forms of secondary HUS. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1523-6838 |
| Relation: |
American Journal of Kidney Diseases; https://iris.unil.ch/handle/iris/138747; serval:BIB_8B36905C32DA; 001277024300001 |
| DOI: |
10.1053/j.ajkd.2023.12.021 |
| Availability: |
https://iris.unil.ch/handle/iris/138747; https://doi.org/10.1053/j.ajkd.2023.12.021 |
| Accession Number: |
edsbas.7E75F24D |
| Database: |
BASE |