Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families.
OBJECTIVE
To describe a new kindred with Clq 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.


CONCLUSIONS
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.
Slingsby
J H
JH
Hammersmith Hospital, London, UK.
Norsworthy
P
P
Pearce
G
G
Vaishnaw
A K
AK
Issler
H
H
Morley
B J
BJ
Walport
M J
MJ
D001483:Base Sequence; D002675:Child, Preschool; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007223:Infant; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009679:Nuclear Family; D017354:Point Mutation / Q000235:genetics*
D015922:Complement C1q