Table 1.
Conventional Complement Deficiencies
| Protein | Gene symbol | MIM ID | Cases / Homozygosity | Disease Associations | References |
|---|---|---|---|---|---|
| Recognition Proteins | |||||
| MBL | MBL2 | 154545 | 5% | infections in immunocompromised individuals | 28,106–108 |
| H-ficolin | FCN3 |
604973, 613860 |
3 | immune deficiency, necrotizing enterocolitis | 40,41 |
| C1q |
C1QA, C1QB, C1QC |
120550, 120570, 120575, 613652 |
43 | SLE-like syndrome, recurrent bacterial infections | 26,33,51 |
| Enzymes | |||||
| MASP-2 | MASP2 | 605102 | 9 | immune deficiency | 37,38 |
| C1r/s |
C1R, C1S |
613785, 120580, 613783, 216950 |
19 | SLE-like syndrome, recurrent bacterial infections | 26,51 |
| C2 | C2 |
613927, 217000 |
1:20,000 | autoimmune disease | 28,32 |
| Factor D | CFD |
134350, 613912 |
<10 | meningococcal and encapsulated bacterial infections | 26 |
| Factor I | CFI |
217030, 610984 |
31 | encapsulated bacterial infections | 109,110 |
| Structural Proteins | |||||
| C3 | C3 |
120700, 613779 |
27 | bacterial infections, SLE-like syndrome | 111,112 |
| C4 |
C4A, C4B |
120810, 120820 |
26 | SLE-like syndrome, encapsulated bacterial infections | 33,51 |
| C5 | C5 |
120900, 609536 |
40 | meningococcal infection | 113,114 |
| C6 | C6 |
217050, 612446 |
>50 | meningococcal infection | 115–117 |
| C7 | C7 |
217070, 610102 |
>50 | meningococcal infection | 116,118,119 |
| C8 |
C8A, C8B, C8G |
120950, 120960, 120930, 613790, 613789 |
>50 | meningococcal infection | 120 |
| C9 | C9 |
120940, 613825 |
1:1,000 (Japan) | meningococcal infection | 46 |
| Control Proteins | |||||
| Properdin | CFP | 300383 | >50 | meningococcal infection | 43 |
| Factor H | CFH |
134370, 609814 |
27 | hemolytic uremic syndrome (HUS), dense deposit disease | 111,121,122 |
| C1-INH | SERPING1 | 606860 | 1:50,000 | hereditary angioedema (HAE) | 33,123 |
| CD11a (LFA-1), CD11b (CR3), CD11c (CR4) /CD181 |
ITGAL, ITGAM, ITGAX, ITGB2 |
153370, 120980, 151510, 600065, 116920 |
1:1,000,000 | leukocyte adhesion deficiency type I (LAD I) | 124,125 |
| CD46 (MCP) | CD46 | 120920 | atypical hemolytic uremic syndrome (aHUS) | 25,126,127 | |
| CD55, CD59 (PIGA)2 |
CD55, CD59, PIGA |
125240, 107271, 612300, 311770, 300818 |
1:1,000,000 | paroxysmal nocturnal hemoglobinuria (PNH) | 128 |
Summary of reported cases of homozygosity for complement-system gene mutations leading to functionally deficient proteins. The proteins in question are given on the left, followed by the gene symbol, the MIM ID number (associated with the gene and/or disease), the number of cases or incidence of homozygosity, and associated clinical findings. The numbers in the last column refer to reviews in which most of the original literature is mentioned or to recent case reports where the literature is discussed. Large ethnical differences are seen for C5, C6, C7, C8, and C9 deficiencies; for example, much higher frequencies of C9 deficiency in Japan as compared to people in western Europe. As is evident, most cases of homozygosity are rare; i.e., below 50 cases. Some are marked “ >50,” which indicates more than 50 but less than 200 cases.1 Concomitant loss of LFA-1, CR3, and CR4 is due to loss of the common CD18 chain.2 Please note that PNH may be caused either directly by a mutation in CD59 or by loss of PIGA function leading to a secondary loss of CD55 and CD59.