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

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.