A complement C5 gene mutation, c.754G>A:p.A252T, is common in the Western Cape, South Africa and found to be homozygous in seven percent of Black African meningococcal disease cases.
We postulate that the C5 defect is not the sole cause of Leiner's disease as has been suggested, but that hypogammaglobulinaemia or other lymphoid deficiency is also required for its expression.
These changes were not due to the C5 deficiency alone as other C5-deficient models did not recapitulate the INSR processing defect; rather, in addition to the mutation in the <i>C5</i> gene, whole genome sequencing revealed an intronic 31-bp deletion in the <i>Insr</i> gene in the B10.D2-<i>Hc<sup>0</sup> H2<sup>d</sup> H2</i>-<i>T18<sup>c</sup></i>/oSnJ model.
Other marker systems excluded from linkage with C5 deficiency included the ceruloplasmin and Duffy loci at a recombination frequency of less than 15%, and the erythrocyte glyoxalase, MN, and Lewis loci at a recombination frequency of less than 5%.