Familial cases of type I complement factor 2 defect (28 BP deletion). Frequency and linked HLA haplotypes in the Spanish population

We describe two familial cases of type I complement factor 2 deficiency and a study of the frequency and HLA associations of the 28 bp deletion of C2 gene responsible for the defect in the Spanish population. Proband in Family 1 (PF1) and proband in Family 2 (FP2) presented several episodes of sepsis and bacteraemia, founding N. meningitidis and S. pneumoniae in cultures. Both probands had very low serum levels of C2 and CH100, and normal levels of Igs and the remaining complement factors. Parents and healthy brother of PF1 showed C2 levels around 50% of the low normal range. The family history of PF2 revealed several cases of meningitis in the maternal branch (aunt, uncle and grandmother). C2 was half-normal level in the affected aunt and the healthy parents. No member of the families showed circulating immunocomplexes, ANA or autoimmune signs or symptoms. The fragment in exon 6 of C2 gene containing the 28 bp deletion was PCR-amplified revealing that both probands were homozygous for the mutation, and family relatives with half-normal levels of serum C2 were heterozygous. In Family 1, the deletion was carried by haplotypes HLA-A*2501 / B*1801/DRB1*1501 and HLA-A*2601/B*1801/DRB1*1501, and in Family 2 it was carried by HLA-A*2501/B*1801/DRB1*1501 and HLA-A*3101/B*1801/DRB1*0901. The study of 406 Spanish healthy controls gave a gene frequency of 0.0037, smaller than those reported in American Caucasoids (0.0070, Sullivan, 1994) or Swedish population (0.0050, Truedsson, 1993).