Tohoku J. Exp. Med., 2012, 227(3)

C3 Glomerulonephritis Associated with a Missense Mutation in the Factor H Gene

KEISUKE SUGIMOTO,¹ SHINSUKE FUJITA,¹ KOUHEI MIYAZAKI,¹ MITSURU OKADA¹ and TSUKASA TAKEMURA¹

¹Department of Pediatrics, Kinki University School of Medicine, Osaka, Japan

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.

keywords —— atypical hemolytic uremic syndrome; complement factor H; C3 glomerulonephritis; dense deposit disease; membranoproliferative glomerulonephritis

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 227, 211-215

Correspondence: Tsukasa Takemura, M.D., Ph.D., Department of Pediatrics, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.

e-mail: tsukasa@med.kindai.ac.jp