Homozygous hereditary C1q deficiency and systemic lupus erythematosus: A new family and the molecular basis of C1q deficiency in three families

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Abstract
Objective. To describe a new kindred with C1q deficiency and to identify the molecular lesions responsible for complete functional C1q deficiency in this and 2 other previously described kindreds. Methods. The A‐, B‐, and C‐chain genes of C1q were amplified by polymerase chain reaction, cloned, and sequenced. The DNA sequence was checked for mutations. Results. Patient 1 had a homozygous G‐to‐A change at codon 6 of the C chain, causing an amino acid change from Gly to Arg. Patient 2 had a homozygous deletion of a C nucleotide at codon 43 of the C‐chain, causing a frame shift, leading to a premature stop codon at codon 108. Patient 3 had a homozygous C‐to‐T mutation at amino acid position 41 of the C chain, resulting in a premature stop codon. Conclusion. In the homozygous state, the mutations are sufficient to cause complete deficiency of C1q. The mutation in patient 1 has been previously reported in a patient of different ethnic origin. A survey of a series of 158 DNA samples from patients with systemic lupus erythematosus showed no other examples of this mutant allele.