CFI
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 I (OMIM# +217030)

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 all, 1997).  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).  Genetics 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 Factor I (CF1, +217030)  
Factor I is a proteolytic enzyme that destroys the hemolytic and immune-adherence activities of cell-bound, activated C3.  The CFI gene contains 13 exons and encodes the 583 amino acid protein, Complement Factor I.  There have been at least 23 reported cases of Factor I-deficient patients.

MORL screening methodology
Oligonucleotide primers have been designed to amplify each exon of CFI.  Because CFI 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: $400

Indications for screening
Screening is offered to persons 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
Caprioli, J. et al.: Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 108(4):1267-79, 2006. Epub 2006 Apr 18.
PubMed ID: 16621965
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Schieppati, A. et al.: Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. The Italian Registry of Haemolytic Uremic Syndrome.  Am Soc Nephrol. 2(11):1640-4, 1992.
PubMed ID: 1610985
PubMed Search

Taylor, C.M. et al.: Clinico-pathological findings in diarrhoea-negative haemolytic uraemic syndrome. Pediatr Nephrol.19(4): 419-25, 2004.  Epub 2004 Feb 24
PubMed ID: 14986082
PubMed Search

Warwicker, P. et al.: Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 53: 836-844, 1998.
PubMed ID : 9551389
PubMed Search