C3
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.

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 may 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).  Identifying the genetic cause of aHUS is extremely important as it can help to direct clinical treatment decisions.

Complement Component 3 (C3 +120700)
Complement component 3 (C3) is an acute phase reactant.  It is induced during acute inflammation and is processed into functional subunits, C3a and C3b.  At least 8 C3 mutations have been identified in persons with aHUS.  The C3 gene contains 41 exons.

MORL screening methodology
Oligonucleotide primers have been designed to amplify each exon of C3.  Amplimers are sequenced directly using overlapping primer sets..

Sensitivity
Sensitivity is greater than 99%.

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

Cost: $1400

Indications for screening
Screening is offered to person with aHUS.

Web Sites

KIDNEEDS (not-for-profit foundation dedicated to the cure of DDD)
www.medicine.uiowa.edu/kidneeds

Foundation for Children with Atypical HUS
http://www.atypicalhus.50megs.com/index.html

References
de Bruijn, M. H. L. et al.  Human complement component C3: cDNA coding sequence and derived primary structure. Proc. Nat. Acad. Sci. 82: 708-712, 19857.
PubMed ID:  2579379
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Fong, K. Y.; et al.  Genomic organization of human complement component C3. Genomics7: 579-586, 1990.
PubMed ID: 2387584
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Frémeaux-Bacchi V, et al.  Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.  Blood. 2008 Dec 15;112(13):4948-52. Epub 2008 Sep 16.
PubMed ID: 18796626
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Loirat C, et al.  Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2008 Nov;23(11):1957-72. Epub 2008 Jul 2.
PubMed ID: 18594873
 PubMed Search