[The genetics of factor XII deficiency].

There are two main forms of factor XII deficiency: patients with immunological cross-reacting material (CRM+) and patients without (CRM-). For 1 case of CRM+ an amino acid substitution (Cys571-->Ser) has been described. We are currently investigating two families of Hageman CRM- trait with the typical hemostaseological pattern: one member with virtually no factor XII activity and antigen, whose sisters and children have about 50% of activity and antigen. To elucidate the genetic defect, primers were synthesized for both exon-intron borders for each of the 14 exons. Polymerase chain reaction (PCR) was performed for each single exon and for any two exons in a row with the intron in between (double-exon screening). We were able to demonstrate that homozygous patients do not have major rearrangements, deletions or insertions of the factor XII gene. To localize the molecular defect, the complete gene was sequenced by cloning the PCR products into pBS. In 1 patient, a single base deletion in exon 12, leading to a nonsense protein, was detected. The propositus was shown to be heterozygous for this defect by a deletion-specific restriction fragment length polymorphism of the PCR product.