Scientific background:

Summary: The membrane protein encoded by this gene is involved in complement activation. Mutations lead to atypical HUS and influence susceptibility to measles.

Molecule: The receptor protein passes the membrane only once. The short N-terminal portion is intracellular. The extracellular portion is of beginning from the C-terminal endcomposed 4 SCR (short consensus repeat) domains and 2 serin-, threonin-, and prolin-rich domains. The SCR are incolved in complement control and therefore sometimes also called complement control proteins (CCP) though they are not proteins but domains.

Molecular anatomy: The complement binding receptor (CD46) is expressed on all human cells except erythrocytes.

Interpretation: Heterozygous mutations may result in either reduced receptor expression on the cell surface (75%) or impaired receptor function (25%). 93% of pathogenetic mutations are located in the 4 SCR (short consensus repeat) domains.
   The penetrance appears to be 54%.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Multiplex Ligation-Dependent Probe Amplification
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Caprioli J et al. (2006) Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.
Richards A et al. (2007) Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome.
Noris M et al. (2003) Familial haemolytic uraemic syndrome and an MCP mutation.
Goodship TH et al. (2004) Mutations in CD46, a complement regulatory protein, predispose to atypical HUS.
Zheng XL et al. (2008) Pathogenesis of thrombotic microangiopathies.
Nürnberger J et al. (2009) Eculizumab for atypical hemolytic-uremic syndrome.