Properdin deficiency in a large Swiss family: identification of a stop codon in the properdin gene, and association of meningococcal disease with lack of the IgG2 allotype marker G2m(n)

Properdin deficiency was demonstrated in three generations of a large Swiss family. The concentration of circulating properdin in affected males was < 0.1 mg/l, indicating properdin deficiency type I. Two of the nine properdin -deficient males in the family had survived meningitis caused by Neisseria meningitidis serogroup B without sequel. Two point mutations were identifie d when the properdin gene in one of the properdin-deficient individuals was investigated by direct solid-phase sequencing of overlapping polymerase ch ain reaction (PCR) products. The critical mutation was found at base 2061 i n exon 4, where the change of cytosine to thymine had generated the stop co don TGA, The other mutation was positioned at base 827 in intron 3. The sto p codon in exon 4 was also demonstrated by standard dideoxy sequencing in t hree additional family members. The question was asked if genetic factors s uch as partial C4 deficiency and IgG allotypes could have influenced suscep tibility to meningococcal disease in the family. No relationship was found between C4 phenotypes and infection. Interestingly, the two properdin-defic ient males with meningitis differed from the other properdin-deficient pers ons in that they lacked the G2m(n) allotype, a marker known to be associate d with poor antibody responses to T-independent antigens. This implies that the consequences of properdin deficiency might partly be determined by ind ependent factors influencing the immune response.