Homozygous hereditary C3 deficiency due to a premature stop codon

Abstract

C3 deficiency in humans is a rare disorder characterized by severe recurrent infections. We identified the mutations responsible for a complete homozygous C3 deficiency. Sequencing of the proband C3 cDNA (5067 bp) revealed the following alterations: (a) a silent G-->A transition at nucleotide 972; (b) a T-->C substitution at nucleotide 1001 resulting in a L314P transition; and (c) a stop codon in exon 13 caused by a G-->A substitution at position 1716. The presence of the same premature termination codon was confirmed in approximately half the clones obtained from the proband's paternal and maternal genomic DNAs. Finally, the proband produced approximately 20-fold less C3 mRNA than the normal control. Therefore, in addition to the fact that no functional protein will be synthesized in the deficient cells, this nonsense mutation may be associated with the low C3 mRNA levels.