Complement Component C1r/c1s Deficiency

Clinical Features

Day et al. (1972) observed 2 sibs with deficiency of C1r (613785). The brother (18 years old) had shown lupus-like features for 5 years. The sister (24 years old) had had arthralgia and recurrent rhinobronchitis from early childhood. Three sibs had died, 1 at age 12 with symptoms like those in the male and 2 in infancy, probably from infection. Laboratory findings suggested the existence of an alternative pathway for activation of the terminal portion of the complement cascade which does not use the usual early components.

Lee et al. (1978) described a family in which 4 of 11 children had absence of C1r and marked deficiency of C1s (120580). Two of the 4 had a syndrome combining discoid lupus erythematosus and nondeforming rheumatoid-like arthritis; 1 had mild nephritis. C1 and C4 deficiencies are more often associated with lupus-like illness than is deficiency of C2. Linkage of HLA and C1 was excluded by the fact that all 4 parental haplotypes were represented in the 4 deficient sibs. Deficiency of C1s has been observed in other cases of C1r absence and may be a secondary effect; however, close linkage of C1s and C1r means that both may be deleted or otherwise deranged.

Loos and Heinz (1986) stated that all reported cases of C1r deficiency also had deficiency of C1s.

A selective deficiency of C1s has been reported; see 613783.

Mapping

Day et al. (1975) found that C1r deficiency is not linked to the HLA region.

Using a panel of human-rodent cell hybrids, Van Cong et al. (1988) assigned the C1r and C1s genes to chromosome 12. In situ hybridization confirmed these assignments and localized the genes to 12p13.