CFB
The Clinical Diagnostics Service of the Molecular Otolaryngology Research Laboratory is a Joint Commission-approved CLIA-accredited diagnostic laboratory that offers mutation screening of several genes.

Complement Factor B (OMIM# *138470)

Atypical Hemolytic-Uremic Syndrome
The clinical manifestations of hemolytic-uremic syndrome (HUS; 235400) include hemolytic anemia, thrombocytopenia and acute renal failure. Most cases are associated with epidemics of diarrhea caused by verocytotoxin-producing bacteria [Escherichia coli O157:H7 (Stx-HUS)].  

 Atypical hemolytic uremic syndrome (aHUS) is a rarer disease.  It is not associated with Stx-HUS infection and neither does it present with watery, bloody diarrhea (Warwicker et al., 1998).  It can be either sporadic or familial, and has an extremely unfavorable prognosis, with about 50% of persons progressing to ESRD and 25% dying during the acute illness; transplantation in many survivors is unsuccessful (Schieppati et al., 1992; Taylor et al., 2004).  Genetic studies have shown that approximately 50% of cases of aHUS are caused by mutations in MCP, CFH and IF (Caprioli et al., 2006). Gain of function mutations in Complement Factor B have been identified in persons with aHUS (Goicoechea de Jorge et a., 2007).  Identifying the genetic cause of aHUS is extremely important as it can help to direct clinical treatment decisions.

Complement Factor B (FB, *138470)
Factor B is a zymogen that carries the catalytic site of the complement alternative pathway convertase C3bBb.  The FB gene contains 18 exons and encodes the 764 amino acid protein, Complement Factor B.  There have been at least two reported cases of Factor B-deficient patients.

MORL screening methodology
Oligonucleotide primers have been designed to amplify each exon of CFB.  Because CFB contains many non-disease causing polymorphisms, it is sequenced directly using overlapping primer sets.

Sensitivity
Sensitivity is greater than 99%.

Turn-around time
Turn around time is approximately 3 months.

Cost: $600

Indications for screening
Screening is offered to persons with aHUS.

References
Caprioli, J.et al.:  Complement hyperactivation may cause atypical haemolytic uraemic syndrome—gain-of-function mutations in Factor B.  Translational Nephrology  22: 2452-2454, 2007.  
PubMed ID:  17510099.
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Goicoechea de Jorge, E et al.:  Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.  PNAS 104(1):240-245, 2007.
PubMed ID: 17182750
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