C1q deficiency is a rare autosomal recessive disorder associated with recurrent skin lesions, chronic infections, systemic lupus erythematosis (SLE; see 152700) or SLE-like diseases. It has also been associated with mesangial proliferative glomerulonephritis. C1q deficiency presents in 2 ... C1q deficiency is a rare autosomal recessive disorder associated with recurrent skin lesions, chronic infections, systemic lupus erythematosis (SLE; see 152700) or SLE-like diseases. It has also been associated with mesangial proliferative glomerulonephritis. C1q deficiency presents in 2 different forms, absent C1q protein or presence of a dysfunctional molecule (summary by Topaloglu et al., 1996).
Thompson et al. (1980) reported C1q deficiency in a 4-year-old son of first-cousin Pakistani parents, who presented with a lupus-like illness and later developed glomerulonephritis. A younger sister, as yet clinically unaffected, had the same complement profile and ... Thompson et al. (1980) reported C1q deficiency in a 4-year-old son of first-cousin Pakistani parents, who presented with a lupus-like illness and later developed glomerulonephritis. A younger sister, as yet clinically unaffected, had the same complement profile and a younger brother had half-normal functional C1 levels. The heterozygous status of both parents, the younger brother, and an older sister was suggested by the presence of double lines on immunochemical analysis of serum from these persons using anti-C1q antiserum; one line showed a reaction of identity with the abnormal C1q of the proband, whereas the other showed a reaction of identity with normal C1q. Hannema et al. (1984) found deficiency of C1q in 2 sisters and a brother. In these persons a dysfunctional C1q molecule was characterized by low molecular weight and antigenic deficiency. In the 2 sisters a systemic lupus erythematosus-like disease began at ages 20 and 23, respectively, resulting in death of 1 of them. All 3 sibs suffered from glomerulonephritis during childhood. The brother was apparently healthy but showed membranous glomerulopathy, stage 1, on renal biopsy. Topaloglu et al. (1996) described 2 sibs with C1q deficiency. Both presented with a photosensitive rash and during follow-up 1 developed SLE with proteinuria in the nephrotic range. The other sib had microscopic hematuria with a history of macroscopic hematuria. Renal biopsies revealed mesangioproliferative glomerulonephritis in 1 and IgA nephropathy in the other. Antibody response to hepatitis B vaccine was normal in affected and unaffected members of the family. Topaloglu et al. (1996) stated that of the 34 reported patients with C1q deficiency, all but one had SLE or an SLE-like illness.
The first molecular lesion in C1q deficiency was reported by McAdam et al. (1988). A homozygous G-to-A transition at nucleotide 150 in the C1QB gene (120570.0001) resulted in a premature stop codon.
In 2 sibs with ... The first molecular lesion in C1q deficiency was reported by McAdam et al. (1988). A homozygous G-to-A transition at nucleotide 150 in the C1QB gene (120570.0001) resulted in a premature stop codon. In 2 sibs with C1q deficiency, Topaloglu et al. (1996) identified homozygosity for a C-T transition in codon 186 of the C1QA gene (120550.0001) that resulted in a gln-to-stop (Q186X) substitution. The mutation was present in heterozygous state in both parents and in 2 unaffected sibs. Topaloglu et al. (1996) stated that the same mutation had been described in an affected member of a Slovakian family with C1q deficiency by Petry et al. (1995). Petry et al. (1997) identified homozygosity for the Q186X mutation in affected members of 3 Turkish families. In 1 family, an asymptomatic sister of the proband was also found to be homozygous for the mutation. Petry et al. (1997) hypothesized that this defective allele is present in the population of southeast Europe and Turkey. In patients with C1q deficiency, Slingsby et al. (1996) identified homozygous mutations in the C1QC gene (120575.0001-120575.0003). - Reviews Rother (1986) gave a summary of reported deficiencies of components of complement. Many examples of deficiencies of C1q were listed, most of them associated with systemic lupus erythematosus or glomerulonephritis.