C3 glomerulonephritis associated with a missense mutation in the factor H gene.
The complement system, the major component of the innate immune functions resisting microbial infection, includes the classical complement pathway, the alternate pathway, and the mannose-binding lectin pathway.  All of these merge at the level of complement component (C) 3.  Complement factor H (CFH), a soluble complement mediator in blood, regulates alternate pathway activation; a conformational change of C3 molecules by C3 convertases leads to an enzyme complex formation resulting in opsonization and cell lysis.  Clinical manifestations arising from CFH gene (CFH) abnormalities include hemolytic uremic syndrome and membranoproliferative glomerulonephritis.  We encountered a 24-year-old woman initially diagnosed with C3 glomerulonephritis associated with persistently low circulating C3.  Definitive diagnosis of C3 glomerulonephritis was made from immunohistologic demonstration of isolated mesangial C3 deposits.  The biopsy specimen showed moderately increased mesangial proliferation, without thickening of the glomerular capillary walls.  Genetic analysis disclosed a homozygous CFH missense mutation, a G-to-T transversion at nucleotide 3,048 in exon 18, resulting in substitution of Asp for Glu at position 936.  A low serum CFH concentration (110 µg/mL) might reflect the consequences of this CFH mutation.  C3 glomerulonephritis is associated with a CFH mutation, the mutation of which results in the unexpected activation of alternate pathway complement with clinical laboratory fluctuations, such as varying reduction of serum CFH and C3.  The finding of a patient with a CFH mutation associated with C3 glomerulonephritis represents an opportunity to expand the phenotypic spectrum of the CFH mutations.
Department of Pediatrics, Kinki University School of Medicine, Osaka, Japan.
Keisuke
K
Sugimoto
Shinsuke
S
Fujita
Kouhei
K
Miyazaki
Mitsuru
M
Okada
Tsukasa
T
Takemura
D001483:Base Sequence; D001706:Biopsy; D002648:Child; D003176:Complement C3 / Q000276:immunology*; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D055815:Young Adult
D003176:Complement C3; D017242:Complement Factor H