Hadas Alfandary1, Miriam Davidovits2,3. 1. Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach, Tikva, Israel, 49202. alfhadas@gmail.com. 2. Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach, Tikva, Israel, 49202. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
BACKGROUND: Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare disease, accounting for 3-5% of all cases of primary nephritic syndrome. We report an uncommon case of familial MPGN type I associated with a new mutation in the complement factor H gene (CFH). METHODS: Clinical data were collected on three siblings with known factor H deficiency who presented with MPGN. All underwent immunological and genetic assays. Their parents and ten healthy adults served as controls for the DNA analysis. RESULTS: All three children presented with recurrent episodes of hematuria and proteinuria, the youngest starting at age 5 months. One child currently has nephrotic syndrome and end-stage renal disease. All of the children were found to be homozygous for a C.262C > A (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a quantitative/functional deficiency of factor H. The parents of the three siblings were found to be heterozygous for the mutation. None of the controls carried this mutation. CONCLUSIONS: Different mutations in CFH may be responsible for different glomerular diseases, including MPGN type I. A modifier gene or an environmental trigger may contribute to this phenotype-genotype discrepancy. Understanding the role of the alternative complement pathway in this disease would allow us to offer these patients more targeted therapy, including a clinical trial of eculizumab.
BACKGROUND: Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare disease, accounting for 3-5% of all cases of primary nephritic syndrome. We report an uncommon case of familial MPGN type I associated with a new mutation in the complement factor H gene (CFH). METHODS: Clinical data were collected on three siblings with known factor H deficiency who presented with MPGN. All underwent immunological and genetic assays. Their parents and ten healthy adults served as controls for the DNA analysis. RESULTS: All three children presented with recurrent episodes of hematuria and proteinuria, the youngest starting at age 5 months. One child currently has nephrotic syndrome and end-stage renal disease. All of the children were found to be homozygous for a C.262C > A (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a quantitative/functional deficiency of factor H. The parents of the three siblings were found to be heterozygous for the mutation. None of the controls carried this mutation. CONCLUSIONS: Different mutations in CFH may be responsible for different glomerular diseases, including MPGN type I. A modifier gene or an environmental trigger may contribute to this phenotype-genotype discrepancy. Understanding the role of the alternative complement pathway in this disease would allow us to offer these patients more targeted therapy, including a clinical trial of eculizumab.
Entities:
Keywords:
Complement dysregulation; Factor H deficiency; Factor H mutation; Familial glomerulonephritis; Membranoproliferative glomerulonephritis
Authors: Timothy H J Goodship; Isabel Y Pappworth; Tibor Toth; Mark Denton; Kris Houlberg; Frances McCormick; David Warland; Iain Moore; Eva-Maria Hunze; Scott J Staniforth; Christine Hayes; Danielle Paixão Cavalcante; David Kavanagh; Lisa Strain; Andrew P Herbert; Christoph Q Schmidt; Paul N Barlow; Claire L Harris; Kevin J Marchbank Journal: Mol Immunol Date: 2012-06-20 Impact factor: 4.407
Authors: Maria Chiara Marinozzi; Lubka T Roumenina; Sophie Chauvet; Alexandre Hertig; Dominique Bertrand; Jérome Olagne; Marie Frimat; Tim Ulinski; Georges Deschênes; Stephane Burtey; Michel Delahousse; Bruno Moulin; Christophe Legendre; Véronique Frémeaux-Bacchi; Moglie Le Quintrec Journal: J Am Soc Nephrol Date: 2017-01-17 Impact factor: 10.121