Complement Component C1s Deficiency

A number sign (#) is used with this entry because selective complement component C1s deficiency can be caused by homozygous mutation in the C1S gene (120580) on chromosome 12p13.

Clinical Features

Inoue et al. (1998) reported a patient with a systemic lupus erythematosus-like syndrome and chronic glomerulonephritis in whom no C1s protein was detectable by immunoblot. By Northern blot and RT-PCR analysis, C1s mRNA was of appropriate size, but only 10% of the level detected in HCS2/8, a human chondrosarcoma cell line. Levels of beta-actin and C1r (216950) mRNA were similar to levels detected in HCS2/8.

In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey et al. (2001) determined that an absence of plasma C1S accounted for a lack of classic complement (CH50) pathway activity. At age 5, the child was alive and well while receiving immunosuppressive drugs daily and penicillin.

Molecular Genetics

Inoue et al. (1998) reported a patient with selective C1s deficiency resulting from a homozygous mutation in the C1S gene (120580.0001).

In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey et al. (2001) detected selective C1S deficiency resulting from a nonsense mutation in exon 12 of the C1S gene (120580.0002). Restriction enzyme analysis showed that the propositus was homozygous for the mutation, while a paternal grandmother, maternal grandfather, and aunts on both sides of the family were heterozygous. The mutation was not detected in systemic lupus erythematosus (152700) patients or unrelated Caucasian controls, including some from the same geographic region.