Complement component
C6 deficiency is a
genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis
infections. This disorder has rarely been diagnosed in the Spanish population. In this work we report the immunochemical and molecular characterization of
complement C6 deficiency in a Spanish patient showing no detectable functional activity of either the classical or alternative
complement pathways and reporting a history of several episodes of
meningococcal meningitis. The levels of individual
complement components C3, C4, C5, C7, C8 and C9 were within the normal range. However, C6 level was low in the patient's serum as measured by radial immunodiffusion. Exon-specific polymerase chain reaction and sequencing of the C6 gene revealed a previously described homozygous single base deletion in exon 6 (c.821delA), leading to a shift in the reading frame that caused the generation of a downstream stop
codon, which, in turn, provoked the truncation of the C6
protein (p.Gln274fs). To our knowledge, this is the first report on the c.821delA mutation in the Spanish population, which has previously only been identified in individuals of African ancestry. Characterization of this mutation was thought interesting in order to elucidate its source and help understand the molecular basis of this uncommon deficiency in our population. Moreover, this report highlights the importance of
complement screening in cases of repeated
meningococcal infections in order to establish its involvement and to consider adequate clinical recommendations such as prophylactic
antibiotics or
meningococcal vaccines and, subsequently, for genetic counselling.