MOLECULAR, GENETIC, AND FUNCTIONAL-ANALYSIS OF HOMOZYGOUS C8 BETA-CHAIN DEFICIENCY IN 2 SIBLINGS

C8 deficiency is associated with an increased susceptibility to neisse rial infections. We present a case of an 11 year old boy who suffered from infection with Neisseria meningitidis. Medical history of the pat ient and his family (it = 5) did not indicate any previous immunodefic iency symptoms. Results from the analysis of phagocyte and lymphocyte functions were within the normal range. No hemolytic activities of the classical (CH50) and the alternative (APH50) pathways of complement w ere measurable, and SC5b-9 protein complexes could not be detected in the patient's plasma. Further analysis by highly sensitive ELISA and f unctional assays revealed a complete deficiency of C8. Upon the recons titution with purified C8 total hemolytic activity could be restored, SDS-PAGE and Western blot analysis established a deficiency of the C8 beta chain. Genetic analysis at the genomic DNA level demonstrated the common C-T mutation in exon 9 of the C8B gene. Family analysis presen ted the older sister with non-detectable function of C8 in serum, both parents with about half-normal C8 titres, and the younger sister with normal C8 function. The parents and both sisters were asymptomatic, a lthough the older of the sisters presented with the same complete C8 b eta-chain deficiency as the patient described. In conclusion: the comm on C-T mutation in the C8B genes is the genetic basis of C8 beta-chain deficiency in two members of this Bosnian family. (C) 1997 Elsevier S cience B.V.