Complement Component 4, Partial Deficiency Of

A number sign (#) is used with this entry because of evidence that the mutation resides in the gene for the C1 inhibitor (C1NH; 606860).

Clinical Features

Muir et al. (1984) described a partial deficiency of C4 in a kindred ascertained through a 26-year-old woman with systemic lupus erythematosus. Six healthy members of the family also had partial deficiency of C4. The inheritance pattern was autosomal dominant with involved persons in 4 sibships of 2 generations (and by inference in a third earlier generation) and with male-to-male transmission. This form of C4 deficiency differs from that in previously reported families in the mode of inheritance, in the marked reduction of C4 levels (2-5% of normal in the proband; 2.4-24.1% of normal in healthy relatives), and in the lack of linkage to HLA, BF and the C4 structural loci.

Wisnieski et al. (1987) found no evidence of hypercatabolism of C4 in metabolic turnover studies which appeared to be compatible with C4 hyposynthesis, even though C4 structural alleles were intact in affected members. In kindred members with decreased C4 levels, Wisnieski et al. (1994) found that after a 15-minute incubation, approximately 50% of serum C1 inhibitor did not complex with and inhibit C1r. However, C1 inhibitor function, as measured by both inhibition of C1s and the ability to form an SDS-stable complex with C1s, was normal in affected kindred members' sera. In addition, approximately half of the C1 inhibitor molecules in affected members' sera appeared to be relatively resistant to cleavage by trypsin. No member of this kindred had ever had angioedema.

Molecular Genetics

In affected members of the kindred originally reported by Muir et al. (1984), Zahedi et al. (1995) identified heterozygosity for an ala443-to-val mutation in the C1 inhibitor gene (606860.0012).