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

Objective. To describe a new kindred with Clq deficiency and to identify the molecular lesions responsible for complete functional Clq 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 Clq. 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.