MOLECULAR-BASES OF C7-DEFICIENCY - 3 DIFFERENT DEFECTS

The molecular basis of C7 deficiency has been investigated in two Iris h families and a number of Israeli families of Moroccan Sephardic jewi sh origin. Exon PCR and sequencing revealed a heterozygous point mutat ion at the 3' splice acceptor site of intron 1 in one Irish family. In the other Irish family, exons 7 and 8 failed to amplify and they were shown to be deleted. Marker haplotype studies of the C6 and C7 gene r egion and Southern blots show that the Irish family with the splice de fect also segregate for the deletion, which is not easily detected in heterozygotes, The Israeli C7-deficient cases all share a C7 haplotype and are homozygous for a mis-sense mutation in exon 9. However, one i ndividual is heterozygous for markers at adjacent C6 loci, showing tha t there has been an intergenic recombination and suggesting that the d eficiency mutation is of appreciable antiquity.