Details

Autor(en) / Beteiligte

• Bienaime, Frank
• Dragon-Durey, Marie-Agnes
• Regnier, Catherine H.
• Nilsson, Sara C.
• Kwan, Wing H.
• Blouin, Jacques
• Jablonski, Mathieu
• Renault, Nicolas
• Rameix-Welti, Marie-Anne
• Loirat, Chantal
• Sautés-Fridman, Catherine
• Villoutreix, Bruno O.
• Blom, Anna M.
• Fremeaux-Bacchi, Veronique

Titel

Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome

Ist Teil von

• Kidney international, 2010-02, Vol.77 (4), p.339-349

Ort / Verlag

Basingstoke: Elsevier Inc

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations in the CFI gene have been characterized. In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI. Their overall clinical outcome was unfavorable, as half died or developed end-stage renal disease after their first syndrome episode. Eight patients with CFI mutations carried at least one additional known genetic risk factor for aHUS, such as a mutation in MCP, CFH, C3 or CFB; a compound heterozygous second mutation in CFI; or mutations in both the MCP and CFH genes. Five patients exhibited homozygous deletion of the Factor H-related protein 1 (CFHR-1) gene. Ten patients with aHUS had one mutation in their CFI gene (Factor I-aHUS), resulting in a quantitative or functional Factor I deficiency. Patients with a complete deletion of the CFHR-1 gene had a significantly higher risk of a bad prognosis compared with those with one Factor I mutation as their unique vulnerability feature. Our results emphasize the necessity of genetic screening for all susceptibility factors in patients with aHUS.