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Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome
L Ying1, Y Katz, M Schlesinger
1Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA.
American Journal of Human Genetics
|December 1, 1999
Summary
A genetic mutation in the complement factor H (CFH) protein causes a rare, early-onset form of atypical hemolytic uremic syndrome (HUS). This mutation impairs CFH protein transport, leading to the disease in a Bedouin family.
Area of Science:
- Genetics
- Molecular Biology
- Nephrology
Background:
- Atypical hemolytic uremic syndrome (HUS) is characterized by hypertension, microangiopathic hemolytic anemia, and acute renal failure.
- Both dominant and recessive inheritance patterns of HUS have been documented.
- Complement factor H (CFH) is implicated in a dominant form of HUS.
Purpose of the Study:
- To investigate the genetic basis of autosomal recessive atypical HUS in a large Bedouin kindred.
- To analyze the role of the complement factor H (CFH) gene in this recessive HUS form.
Main Methods:
- Genetic linkage analysis was performed using markers near the CFH gene.
- Mutation analysis of the CFH coding region was conducted.
- Functional studies assessed the expression, synthesis, and transport of the mutant CFH protein.
Main Results:
- Linkage analysis confirmed the association between the HUS disorder and the CFH gene region.
- A single missense mutation was identified in the CFH coding region.
- The mutant CFH protein was expressed and synthesized but exhibited abnormal intracellular transport and secretion.
Conclusions:
- This study identifies a novel association between the CFH protein and recessive, early-onset, atypical HUS.
- A CFH mutation affecting intracellular trafficking and secretion is implicated in the pathogenesis of HUS.
- This finding expands the understanding of HUS genetics and the role of CFH in complement regulation.