Membrane Cofactor Protein (MCP)
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.

MCP (MCP, +120920)
The MCP gene contains 14 exons that encode the 392 amino acid protein Membrane Cofactor Protein (MCP; CD46).  MCP is a locally synthesized membrane bound complement regulator with co-factor activity for Factor I (CFI; 217030)-mediated cleavage of C3b and C4b.  Over 30 mutations in the MCP gene have been identified in persons with aHUS.  Mutation screening of MCP is indicated in persons with aHUS.

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

MORL screening methodology
Oligonucleotide primers have been designed to amplify each exon of MCP.  Because MCP 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: $450

Indications for screening
Screening is offered to persons with aHUS.

Web Sites
Screening is offered to persons with aHUS.

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

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