Table 4

Molecular characterisation of the genetics defects

Patient no.	Codon change	Protein domain	Mutation characteristics
HUS, haemolytic uraemic syndrome; LDLr, low density lipoprotein receptor; MCP, membrane cofactor protein.
MCP gene, exon 11 encodes for the transmembrane domain 1. The amino acid numbering refers to the start codon of the sequence after the peptide signal (Met +34).
FI gene, the nucleotide number one is nucleotide located 29 before the start of the peptide signal sequence. The start codon of the sequence after the peptide signal was used as the first amino acid of the protein.
FH gene, the nucleotide number one is nucleotide located 73 before the ATG used as the first amino acid of the protein.
CFH gene
15	R1210C	SCR20	Located in SCR20. Previously reported in several unrelated patients with HUS. Is associated with a reduced binding of FH to the central complement component C3b/C3d, as well as to endothelial cells.^10,¹⁹


16	P76-X	SCR2	One nucleotide deletion in exon 2 leading to half antigenic levels of FH. Previously reported in more than 10 cases of HUS.
6	G650V	SCR 11	Located in SCR 11 close to the C3b binding domain. Other mutations in the same domain have been reported in two patients with atypical HUS.^6,²⁰

CFI gene
17	A222G	LDLRA-1	Both mutations are located in two LDLr domains in the heavy chain of FI. The LDLr domains are highly conserved cysteine-rich regions possibly involved in FI ligand binding. These mutations have been reported in 10 patients with HUS.^17,^21,²²
18	G243D	LDLRA-2
MCP gene
7	V181M + A304V	SCR 3	Two heterozygous mutations associated with normal expression of the protein at the surface of granulocytes. c.747G>A is located in the CCP-3 domain which is highly implicated in the active site of the protein (binding to C4b and C3b), as previously demonstrated using mutagenesis.²³ A304V has been reported in patients with HUS.²¹