A hereditary C3 deficiency due to aberrant splicing of exon 10

Hereditary C3 deficiency in a 22-year-old woman was studied. Previous works indicated that C3 could not be detected in the serum of such a patient by enzyme immunoassay. In this study, we demonstrated that C3 genes of this patient and her parents have no gross structural aberration. However, C3 mRNA was almost not detectable in the skin fibroblasts of this patient. The activity of the patient's C3 upstream regulatory elements was tested and showed no functional abnormality. Using reverse-transcriptase polymerase chain reaction (RT-PCR) to amplify RNA from LPS-stimulated patient's fibroblasts, two shorter cDNAs within C3 exon 8 to exon 12 were noted. DNA sequence analysis of the RT-PCR products revealed that one deleted 116 nucleotides of the full exon 10 and the other deleted 34 nucleotides in the 3' region of exon 10. A single base substitution (G to T) in the splice donor site of intron 10 was identified. This aberrant splicing involving exon 10 could result in translational pretermination at exon 11. Thus, this mutation provided the molecular basis for the deficiency of C3 in the patient.